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‣ STABILITY OF PSYCHIATRIC DIAGNOSIS

Ray, R.; Roychowdhury, J.
Fonte: Medknow Publications Publicador: Medknow Publications
Tipo: Artigo de Revista Científica
Publicado em //1984 Português
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Eighty five charts of patients whose diagnoses have changed at least once between 1977 and 1981 (unstable) were compared with another randomly chosen charts where diagnosis during the subsequent admissions remained unchanged (stable). Seventy six percent of the changes occurred from one to the other diagnostic category and remained so. Seventy three percent of Schizophrenics, 77.5% of Manics, 45% of Depressives and only 31% the Neurotics retained their original diagnosis. More Schizophrenics became Manics rather than the reverse. No statistically significant differences were found regarding changes between the other diagnostic categories. Unstable group had lesser frequency of admissions before the index admission and were more often readmitted.

‣ PSYCHIATRIC MORBIDITY AND THE MENOPAUSE

Prakash, Indira Jai; Murthy, Vinoda N.
Fonte: Medknow Publications Publicador: Medknow Publications
Tipo: Artigo de Revista Científica
Publicado em //1981 Português
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A sample consisting of Menopausal, pre menopausal and post menopausal women in the age range of 36 to 50 years was studied using a two stage screening procedure for identifying and assessing psychiatric morbidity. The screening device, General Health questionnaire (GHQ) identified 21 of the 105 women studied as ‘possible cases’. On further interviews using standard psychiatric interview (SPI) a higher proportion of menopausal women were found to be psychiatrically ill. The predominant symptom in the Menopausal group was depression. Both menopausal women and women who had undergone hysterectomy (surgical menopause) received higher mean ratings on SPI. The inter-rater reliability of SPI was found to be high and was comparable to those reported by original authors.

‣ Adenovirus–Retrovirus Hybrid Vectors Achieve Highly Enhanced Tumor Transduction and Antitumor Efficacy In Vivo

Kubo, Shuji; Haga, Kazunori; Tamamoto, Atsuko; Palmer, Donna J; Ng, Philip; Okamura, Haruki; Kasahara, Noriyuki
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Murine leukemia virus (MLV)–based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ...

‣ Anterior versus posterior surgery for multilevel cervical myelopathy, which one is better? A systematic review

Liu, Tao; Xu, Wen; Cheng, Tao; Yang, Hui-Lin
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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The objective of the study is to perform a systematic review to compare the clinical outcomes and complications of anterior surgery with posterior surgery for multilevel cervical myelopathy (MCM). MEDLINE, EMBASE databases and other databases were searched for all the relevant original articles published from January 1991 to November 2009 comparing anterior with posterior surgery for MCM. Subgroup analysis was performed according to the follow-up years. The following end points were mainly evaluated: final follow-up JOA (Japanese Orthopaedic Association) scale, recovery rate and complication outcomes. Ten articles fulfilled all inclusion criteria. For multilevel CSM patients, the final follow-up JOA score for the anterior group was significantly higher than the posterior group (p < 0.05, WMD 0.83 [0.24, 1.43]) in the ‘follow-up time ≤5 years’ subgroup, but had no significant differences in the ‘follow-up time >5 years’ subgroup (p > 0.05). The recovery rate for the anterior group was significantly higher than the posterior group (p < 0.05, WMD 10.08 [1.39, 18.78]) in the ‘follow-up time ≤5 years’ subgroup. No study reported the recovery rate for the follow-up time >5 years. For multilevel OPLL patients, the final follow-up JOA score and recovery rate for the anterior group were both significantly higher than the posterior group in the ‘follow-up time ≤5 years’ subgroup (p < 0.05...

‣ Contributions to the Content Analysis of Gender Roles: An Introduction to a Special Issue

Rudy, Rena M.; Popova, Lucy; Linz, Daniel G.
Fonte: Springer US Publicador: Springer US
Tipo: Artigo de Revista Científica
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This special issue on gender-related content analysis is the second of two parts (see Rudy et al. 2010b). The current special issue is more diverse than was the first in the number of countries that are represented and in the variety of media genres and content types that are included. The primary aim of this paper is to outline some of the contributions of the individual papers in this second special issue. Some of these advancements and innovations include (a) examining underresearched measures, countries, time spans, sexual orientations, and individual media programs; (b) addressing both international and intranational differences in gender-role portrayals; (c) comparing multiple content formats within the same media unit; (d) updating past findings to take into consideration the current media landscape; (e) employing established measures in novel ways and novel contexts; (f) uncovering limitations in established intercultural measures and media-effects theories; (g) suggesting variables that could predict additional differences in gender-role portrayals; (h) adopting virtually identical methods and measures across distinct content categories in order to facilitate comparisons; (i) conducting multiple tests of a given hypothesis; (j) examining...

‣ High frequencies of leukemia stem cells in poor-outcome childhood precursor-B acute lymphoblastic leukemias

Morisot, S; Wayne, A S; Bohana-Kashtan, O; Kaplan, I M; Gocke, C D; Hildreth, R; Stetler-Stevenson, M; Walker, R L; Davis, S; Meltzer, P S; Wheelan, S J; Brown, P; Jones, R J; Shultz, L D; Civin, C I
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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In order to develop a xenograft model to determine the efficacy of new therapies against primary human precursor-B acute lymphoblastic leukemia (ALL) stem cells (LSCs), we used the highly immunodeficient non-obese diabetic (NOD).Cg-PrkdcscidIL2rgtmlWjl/SzJ (NOD-severe combined immune deficient (scid) IL2rg−/−) mouse strain. Intravenous transplantation of 2 of 2 ALL cell lines and 9 of 14 primary ALL cases generated leukemia-like proliferations in recipient mice by 1–7 months after transplant. Leukemias were retransplantable, and the immunophenotypes, gene rearrangements and expression profiles were identical or similar to those of the original primary samples. NOD-scid mice transplanted with the same primary samples developed similar leukemias with only a slightly longer latency than did NOD-scid-IL2Rg−/− mice. In this highly sensitive NOD-scid-IL2Rg−/−-based assay, 1–100 unsorted primary human ALL cells from five of five tested patients, four of whom eventually experienced leukemia relapse, generated leukemias in recipient mice. This very high frequency of LSCs suggests that a hierarchical LSC model is not valuable for poor-outcome ALL.

‣ Viral nanoparticles as macromolecular devices for new therapeutic and pharmaceutical approaches

Grasso, Simone; Santi, Luca
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 06/07/2010 Português
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Viral nanoparticles are molecular cages derived from the assembly of viral structural proteins. They bear several peculiar features as proper dimensions for nanoscale applications, size homogeneity, an intrinsic robustness, a large surface area to mass ratio and a defined, repetitive and symmetric macromolecular organization. A number of expression strategies, using various biological systems, efficiently enable the production of significant quantities of viral nanoparticles, which can be easily purified. Genetic engineering and in vitro chemical modification consent to manipulate of the outer and inner surface of these nanocages, allowing specific changes of the original physico-chemical and biological properties. Moreover, several studies have focused on the in vitro disassembly/reassembly and gating of viral nanoparticles, with the aim of encapsulating exogenous molecules inside and therefore improving their potential as containment delivery devices. These technological progresses have led research to a growing variety of applications in different fields such as biomedicine, pharmacology, separation science, catalytic chemistry, crop pest control and material science. In this review we will focus on the strategies used to modify the characteristics of viral nanoparticles and on their use in biomedicine and pharmacology.

‣ Diffusion tensor imaging in the cervical spinal cord

Song, Ting; Chen, Wen-Jun; Yang, Bo; Zhao, Hong-Pu; Huang, Jian-Wei; Cai, Ming-Jin; Dong, Tian-Fa; Li, Tang-Sheng
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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There are discrepancy between MR findings and clinical presentations. The compressed cervical cord in patients of the spondylotic myelopathy may be normal on conventional MRI when it is at the earlier stage or even if patients had severe symptoms. Therefore, it is necessary to take a developed MR technique—diffusion tensor imaging (DTI)—to detect the intramedullary lesions. Prospective MR and DTI were performed in 53 patients with cervical compressive myelopathy and twenty healthy volunteers. DTI was performed along six non-collinear directions with single-shot spin echo echo-planar imaging (EPI) sequence. Intramedullary apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in four segments (C2/3, C3/4, C4/5, C5/6) for volunteers, in lesions (or the compressed cord) and normal cord for patients. DTI original images were processed to produce color DTI maps. In the volunteers’ group, cervical cord exhibited blue on the color DTI map. FA values between four segments had a significant difference (P < 0.01), with the highest FA value (0.85 ± 0.03) at C2/3 level. However, ADC value between them had no significant difference (P > 0.05). For patients, only 24 cases showed hyperintense on T2-weighted image...

‣ A dynamic in vitro BBB model for the study of immune cell trafficking into the central nervous system

Cucullo, Luca; Marchi, Nicola; Hossain, Mohammed; Janigro, Damir
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Although there is significant evidence correlating overreacting or perhaps misguided immune cells and the blood–brain barrier (BBB) with the pathogenesis of neuroinflammatory diseases, the mechanisms by which they enter the brain are largely unknown. For this purpose, we revised our humanized dynamic in vitro BBB model (DIV-BBBr) to incorporate modified hollow fibers that now feature transmural microholes (2 to 4 μm ∅) allowing for the transendothelial trafficking of immune cells. As with the original model, this new DIV-BBBr reproduces most of the physiological characteristics of the BBB in vivo. Measurements of transendothelial electrical resistance (TEER), sucrose permeability, and BBB integrity during reversible osmotic disruption with mannitol (1.6 mol/L) showed that the microholes do not hamper the formation of a tight functional barrier. The in vivo rank permeability order of sucrose, phenytoin, and diazepam was successfully reproduced in vitro. Flow cessation followed by reperfusion (Fc/Rp) in the presence of circulating monocytes caused a biphasic BBB opening paralleled by a significant increase of proinflammatory cytokines and activated matrix metalloproteinases. We also observed abluminal extravasation of monocytes but only when the BBB was breached. In conclusion...

‣ EGFR Gene Overexpression Retained in an Invasive Xenograft Model by Solid Orthotopic Transplantation of Human Glioblastoma Multiforme Into Nude Mice

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan
Fonte: Informa Healthcare Publicador: Informa Healthcare
Tipo: Artigo de Revista Científica
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Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

‣ UniProt Knowledgebase: a hub of integrated protein data

Magrane, Michele; Consortium, UniProt
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 29/03/2011 Português
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The UniProt Knowledgebase (UniProtKB) acts as a central hub of protein knowledge by providing a unified view of protein sequence and functional information. Manual and automatic annotation procedures are used to add data directly to the database while extensive cross-referencing to more than 120 external databases provides access to additional relevant information in more specialized data collections. UniProtKB also integrates a range of data from other resources. All information is attributed to its original source, allowing users to trace the provenance of all data. The UniProt Consortium is committed to using and promoting common data exchange formats and technologies, and UniProtKB data is made freely available in a range of formats to facilitate integration with other databases.

‣ Full-endoscopic technique for anterior cervical discectomy and interbody fusion: 5-year follow-up results of 67 cases

Yao, Nuzhao; Wang, Cheng; Wang, Wenjun; Wang, Lushan
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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With minimally invasive technique becoming more popular, endoscopic operations such as arthroscopy or laparoscopy have become the standard of care in several other areas. In this study, we evaluated the 5-year follow-up outcomes of anterior cervical (Ahn et al. in Photomed Laser Surg 23:362–368, 2005) discectomy and interbody fusion (ACDF) performed via endoscopic approach. Sixty-seven patients who underwent anterior cervical discectomy and cage fusion performed using endoscopic technique were followed for at least 5 years. We reviewed the clinical and radiographic records of these patients. The postoperative radiographic measures accessed were the anterior intervertebral height (AIH) and the lordosis angle (LDA). Clinical outcomes were determined using the previously validated Japanese Orthopaedic Association (JOA) and the pain visual analog scale (VAS). Patients included had a minimal follow-up period of 5 years and based on the outcomes criteria (JOA, VAS), 86.6% of patients reported excellent or good results. The AIH increased on average 18.7% of the original height (p < 0.01), and the LDA were more physiologic at final follow-up. Of the 67 cases, there was no segmental instability, and the bone fusion rate was 100%. One patient required revision open ACDF due to adjacent segment disc herniation 6 years postoperatively. There were no intraoperative complications...

‣ Resistance and resilience of benthic biofilm communities from a temperate saltmarsh to desiccation and rewetting

McKew, Boyd A; Taylor, Joe D; McGenity, Terry J; Underwood, Graham J C
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Periods of desiccation and rewetting are regular, yet stressful events encountered by saltmarsh microbial communities. To examine the resistance and resilience of microbial biofilms to such stresses, sediments from saltmarsh creeks were allowed to desiccate for 23 days, followed by rewetting for 4 days, whereas control sediments were maintained under a natural tidal cycle. In the top 2 mm of the dry sediments, salinity increased steadily from 36 to 231 over 23 days, and returned to seawater salinity on rewetting. After 3 days, desiccated sediments had a lower chlorophyll a (Chl a) fluorescence signal as benthic diatoms ceased to migrate to the surface, with a recovery in cell migration and Chl a fluorescence on rewetting. Extracellular β-glucosidase and aminopeptidase activities decreased within the first week of drying, but increased sharply on rewetting. The bacterial community in the desiccating sediment changed significantly from the controls after 14 days of desiccation (salinity 144). Rewetting did not cause a return to the original community composition, but led to a further change. Pyrosequencing analysis of 16S rRNA genes amplified from the sediment revealed diverse microbial responses, for example desiccation enabled haloversatile Marinobacter species to increase their relative abundance...

‣ The pharmacological effects of the thermostabilising (m23) mutations and intra and extracellular (β36) deletions essential for crystallisation of the turkey β-adrenoceptor

Baker, Jillian G.; Proudman, Richard G. W.; Tate, Christopher G.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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The X-ray crystal structure of the turkey β-adrenoceptor has recently been determined. However, mutations were introduced into the native receptor that was essential for structure determination. These may cause alterations to the receptor pharmacology. It is therefore essential to understand the effects of these mutations on the pharmacological characteristics of the receptor. This study examined the pharmacological effects of both the m23 mutations and the β36 deletions, both alone and then in combination in the β36–m23 mutant used in the crystallisation and structure determination of the turkey β-adrenoceptor. Stable CHO-K1 cell lines were made of each of the receptor mutants and the affinity and efficacy of ligands assessed by 3H-CGP 12177 whole cell ligand binding, 3H-cAMP accumulation, and CRE-SPAP gene transcription assays. The m23 mutations reduced affinity for agonists, partial agonists and neutral antagonists by about tenfold whilst the β36 deletions alone had no effect on ligand affinity. Both sets of changes appeared to reduce the agonist activation of the receptor. Both the m23 and the β36 receptors retained two active agonist-induced receptor conformations similar to that of the original tβtrunc receptor. The combined β36–m23 receptor bound ligands with similar affinity to the m23 receptor; however...

‣ Calpain-mediated cleavage of Beclin-1 and autophagy deregulation following retinal ischemic injury in vivo

Russo, R; Berliocchi, L; Adornetto, A; Varano, G P; Cavaliere, F; Nucci, C; Rotiroti, D; Morrone, L A; Bagetta, G; Corasaniti, M T
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Autophagy is the major intracellular degradation pathway that regulates long-lived proteins and organelles turnover. This process occurs at basal levels in all cells but it is rapidly upregulated in response to starvation and cellular stress. Although being recently implicated in neurodegeneration, it remains still unclear whether autophagy has a detrimental or protective role. In this study, we investigated the dynamics of the autophagic process in retinal tissue that has undergone transient ischemia, an experimental model that recapitulates features of ocular pathologies, including glaucoma, anterior ischemic optic neuropathy and retinal vessels occlusion. Retinal ischemia, induced in adult rats by increasing the intraocular pressure, was characterized by a reduction in the phosphatidylethanolamine-modified form of LC3 (LC3II) and by a significant decrease in Beclin-1. The latter event was associated with a proteolytic cleavage of Beclin-1, leading to the accumulation of a 50-kDa fragment. This event was prevented by intravitreal treatment with the non-competitive N-methyl-D-aspartate antagonist MK801 and calpain inhibitors or by calpain knockdown. Blockade of autophagy by pharmacological inhibition or Beclin-1 silencing in RGC-5 increased cell death...

‣ Relationship between bacterial diversity and function under biotic control: the soil pesticide degraders as a case study

Monard, Cécile; Vandenkoornhuyse, Philippe; Le Bot, Barbara; Binet, Françoise
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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In soil, the way biotic parameters impact the relationship between bacterial diversity and function is still unknown. To understand these interactions better, we used RNA-based stable-isotope probing to study the diversity of active atrazine-degrading bacteria in relation to atrazine degradation and to explore the impact of earthworm-soil engineering with respect to this relationship. Bulk soil, burrow linings and earthworm casts were incubated with 13C-atrazine. The pollutant degradation was quantified by liquid chromatography–mass spectrometry for 8 days, whereas active atrazine degraders were identified at 2 and 8 days by sequencing the 16S ribosomal RNA in the 13C-RNA fractions from the three soil microsites. An original diversity of atrazine degraders was found. Earthworm soil engineering greatly modified the taxonomic composition of atrazine degraders with dominance of α-, β- and γ-proteobacteria in burrow linings and of Actinobacteria in casts. Earthworm soil bioturbation increased the γ-diversity of atrazine degraders over the soil microsites generated. Atrazine degradation was enhanced in burrow linings in which primary atrazine degraders, closely related to Pelomonas aquatica, were detected only 2 days after atrazine addition. Atrazine degradation efficiency was not linearly related to the species richness of degraders but likely relied on keystone species. By enhancing soil heterogeneity...

‣ Neither IL-17A mRNA Nor IL-17A Protein Are Detectable in Langerhans Cell Histiocytosis Lesions

Peters, Tricia L; McClain, Kenneth L; Allen, Carl E
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Langerhans cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions including CD207+/CD1a+ dendritic cells that can result in significant morbidity and mortality. The etiology of LCH remains speculative, and neoplastic and inflammatory origins have been debated for decades. A recent study identified abundant interleukin-17 (IL-17A) protein in dendritic cells in LCH lesions as well as in plasma from patients with active disease. Furthermore, it identified dendritic cells as a novel source of IL-17A expression. However, subsequent studies from our research group failed to identify any IL-17A gene expression from CD207+ dendritic cells or CD3+ T cells in LCH lesions. In this study, further investigation once again fails to identify any cells in LCH lesions with IL-17A gene expression. Furthermore, IL-17A antigen is undetectable in LCH lesion lysates with western blotting, immunoprecipitation, spectral analysis, and enzyme-linked immunosorbent assay (ELISA). Western blots, immunoprecipitation, and ELISA experiments also demonstrate that antibodies used in original studies that established the IL-17A hypothesis for pathogenesis of LCH recognize nonspecific proteins. We conclude that evidence for IL-17A as a significant factor in LCH remains inadequate and clinical trials targeting IL-17A remain unjustified.

‣ Development of an All-in-One Lentiviral Vector System Based on the Original TetR for the Easy Generation of Tet-ON Cell Lines

Benabdellah, Karim; Cobo, Marién; Muñoz, Pilar; Toscano, Miguel G.; Martin, Francisco
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 18/08/2011 Português
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Lentiviral vectors (LVs) are considered one of the most promising vehicles to efficiently deliver genetic information for basic research and gene therapy approaches. Combining LVs with drug-inducible expression systems should allow tight control of transgene expression with minimal side effect on relevant target cells. A new doxycycline-regulated system based on the original TetR repressor was developed in 1998 as an alternative to the TetR-VP16 chimeras (tTA and rtTA) to avoid secondary effects due to the expression of transactivator domains. However, previously described TetR-based systems required cell cloning and/or antibiotic selection of tetracycline-responsive cells in order to achieve good regulation. In the present manuscript we have constructed a dual Tet-ON system based on two lentiviral vectors, one expressing the TetR through the spleen focus forming virus (SFFV) promoter (STetR) and a second expressing eGFP through the regulatable CMV-TetO promoter (CTetOE). Using these vectors we have demonstrated that the TetR repressor, contrary to the reverse transactivator (rtTA), can be expressed in excess to bind and modulate a high number of TetO operons. We have also showed that this dual vector system can generate regulatable bulk cell lines (expressing high levels of TetR) that are able to modulate transgene expression either by varying doxycycline concentration and/or by varying the amount of CTetOE vector genomes per cell. Based on these results we have developed a new all-in-one lentiviral vector (CEST) driving the expression of TetR through the SFFV promoter and the expression of eGFP through the doxycycline-responsive CMV-TetO operon. This vector efficiently produced Tet-ON regulatable immortalized (293T) and primary (human mesenchymal stem cells and human primary fibroblasts) cells. Bulk doxycycline-responsive cell lines express high levels of the transgene with low amount of doxycycline and are phenotypically indistinct from its parental cells.

‣ The organotelluride catalyst LAB027 prevents colon cancer growth in the mice

Coriat, R; Marut, W; Leconte, M; Ba, L B; Vienne, A; Chéreau, C; Alexandre, J; Weill, B; Doering, M; Jacob, C; Nicco, C; Batteux, F
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Organotellurides are newly described redox-catalyst molecules with original pro-oxidative properties. We have investigated the in vitro and in vivo antitumoral effects of the organotelluride catalyst LAB027 in a mouse model of colon cancer and determined its profile of toxicity in vivo. LAB027 induced an overproduction of H2O2 by both human HT29 and murine CT26 colon cancer cell lines in vitro. This oxidative stress was associated with a decrease in proliferation and survival rates of the two cell lines. LAB027 triggered a caspase-independent, ROS-mediated cell death by necrosis associated with mitochondrial damages and autophagy. LAB027 also synergized with the cytotoxic drug oxaliplatin to augment its cytostatic and cytotoxic effects on colon cancer cell lines but not on normal fibroblasts. The opposite effects of LAB027 on tumor and on non-transformed cells were linked to differences in the modulation of reduced glutathione metabolism between the two types of cells. In mice grafted with CT26 tumor cells, LAB027 alone decreased tumor growth compared with untreated mice, and synergized with oxaliplatin to further decrease tumor development compared with mice treated with oxaliplatin alone. LAB027 an organotelluride catalyst compound synergized with oxaliplatin to prevent both in vitro and in vivo colon cancer cell proliferation while decreasing the in vivo toxicity of oxaliplatin. No in vivo adverse effect of LAB027 was observed in this model.

‣ Variation of selfing rate and inbreeding depression among individuals and across generations within an admixed Cedrus population

Ferriol, M; Pichot, C; Lefèvre, F
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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We investigated the variation and short-term evolution of the selfing rate and inbreeding depression (ID) across three generations within a cedar forest that was established from admixture ca 1860. The mean selfing rate was 9.5%, ranging from 0 to 48% among 20 seed trees (estimated from paternally inherited chloroplast DNA). We computed the probability of selfing for each seed and we investigated ID by comparing selfed and outcrossed seeds within progenies, thus avoiding maternal effects. In all progenies, the germination rate was high (88–100%) and seedling mortality was low (0–12%). The germination dynamics differed significantly between selfed and outcrossed seeds within progenies in the founder gene pool but not in the following generations. This transient effect of selfing could be attributed to epistatic interactions in the original admixture. Regarding the seedling growth traits, the ID was low but significant: 8 and 6% for height and diameter growth, respectively. These rates did not vary among generations, suggesting minor gene effects. At this early stage, outcrossed seedlings outcompeted their selfed relatives, but not necessarily other selfed seedlings from other progenies. Thus, purging these slightly deleterious genes may only occur through within-family selection. Processes that maintain a high level of genetic diversity for fitness-related traits among progenies also reduce the efficiency of purging this part of the genetic load.