MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene. Most endemic BL and a fraction of sporadic BL are associated with Epstein-Barr virus (EBV) infection. The currently accepted mechanism is that EBV is the BL-causing agent inducing MYC translocation. Herein we show that the EBV receptor, CR2 (also called CD21), is a direct MYC target gene. This is based on several pieces of evidence: MYC induces CR2 expression in both proliferating and arrested cells and in the absence of protein synthesis, binds the CR2 promoter and transactivates CR2 in an E-box-dependent manner. Moreover, using mice with conditional MYC ablation we show that MYC induces CR2 in primary B cells. Importantly, modulation of MYC levels directly correlates with EBV's ability of infection in BL cells. Altogether, in contrast to the widely accepted hypothesis for the correlation between EBV and BL, we propose an alternative hypothesis in which MYC dysregulation could be the first event leading to the subsequent EBV infection.

Skrjabinodon castillensis (Nematode: Pharyngodonidae) parasitizing Liolaemus gracielae lizard (Squamata: Iguania: Liolaemidae) from Argentina.

Skrjabinodon castillensis is mentioned and illustrated here, based on specimens found in the large intestines of Liolaemus gracielae (Squamata: Liolaemidae) collected in San Juan province, Argentina. The species found is assigned to Skrjabinodon based lateral alae present in males. Lateral alae beginning midway between lips and nerve ring and ending just posterior to first pair of caudal papillae. In males, caudal alae absent, paired caudal papillae present. The species recorded in this study differs from all other species assigned to Skrjabinodon by morphology and number of tail filament spines. Skrjabinodon castillensis is the ninth species from the Neotropical realm and the only species of this genus known from Argentina.

High reproductive effort in a vulnerable lizard from high altitudes in Argentina: Reproductive biology and sexual dimorphism in Phymaturus extrilidus.

Reproductive biology is fundamental to understanding the ecology and evolution of lizards which, in turn, is essential for the definition of the species´ conservation status. We studied life-history traits related to the reproduction of the Phymaturus extrilidus lizard, including the male and female reproductive cycles, litter size, mean annual reproductive output, reproductive effort, sexual maturity size and sexual dimorphism, body condition, and fat body cycles. We found sexual dimorphism in size and shape, supporting the hypotheses of sexual and fecundity selection. Females exhibited biennial reproductive cycles synchronous with the annual prenuptial male cycle, adjusted for the maturation of the vitellogenic follicles of females. Females of P. extrilidus have the highest mean annual reproductive output (MARO=1.14) recorded in Phymaturus, and this is accompanied by the highest reproductive effort (C=0.28, C energetic =0.31). Births occur from late summer to early autumn. The female reproductive cycle, strictly biennial, like all species of the P. palluma group, and the vitellogenesis in particular, appear to be limited by body condition and the amount of fat body stored. This study presents the fundamental reproductive traits of P. extrilidus that can provide valuable information to be used in the evaluation of the conservation status of this species.

Skrjabinodon castillensis n. sp. (Nematoda:Pharyngodonidae) from the Homonota horrida and H.darwinii (Squamata: Phyllodactylidae) from Argentina and key for the Neotropical species of the genus Skrjabinodon.

Skrjabinodon castillensis n. sp. is described and illustrated here, based on specimens found in the large intestines of Homonota horrida (province San Juan) and Homonota darwinii (province Neuquén) (Squamata: Phyllodactylidae) from Argentina. The new species is assigned to Skrjabinodon based lateral alae present in males, absent in females. Lateral alae beginning midway between lips and nerve ring and ending just posterior to first pair of caudal papillae. Females with vulva near esophageal bulb. In males, caudal alae absent, paired caudal papillae present. Skrjabinodon castillensis n. sp. represents the 9th species from the Neotropical realm. The new species differs from all other species assigned to Skrjabinodon by morphology of tail filament and number of tail filament spines. Skrjabinodon castillensis n. sp. is the only species of this genus known from Argentina. A key to the species of Skrjabinodon in the Neotropical realm is provided.

Offseason Medfly Trapping Using Makeshift Fruit-Based and Wine Vinegar Baits.

Development of cost-effective traps and attractants is important for sustainable pest management. In the case of the Medfly, Ceratitis capitata Wiedemann, a worldwide pest of fruit production, recent interest in development of mass trapping strategies and low-cost easy-to-get artisanal traps for resource poor grower use has prompted renewed interest in research on attractants and traps. Additionally, such interest is also rooted on the need for effective female attractants to monitor wild population dynamics under male-only sterile fly releases. Response of wild flies and sterile males to makeshift traps (modified polyethylene terephthalate (pet) bottles) baited with fruit juice and wine vinegar dilutions with and without the addition of sugar revealed that a 50% dilution of wine vinegar or sweetened orange juice were more attractive than the standard Torula baits during the offseason (after harvest) in a peach orchard in arid irrigated valleys of San Juan Argentina. Such results suggest that volatiles from orange peel and juice are good candidates for development of Medfly attractants, and that pet bottles baited with sweetened orange juice and wine vinegar may be used by small growers and homeowners as low-cost-effective traps for Medfly control. Our results also suggest that Medfly response to food-based and fruit-based volatiles may be seasonally dynamic, a finding with important pest management implications.

Uso y selección de microhábitat en un ensamble de anuros del Chaco Serrano de Argentina

Introducción: El estudio de las estrategias de uso y partición del recurso espacial resulta importante para entender los mecanismos de coexistencia de especies de anfibios simpátricas, más aún cuando existen variaciones temporales en la disponibilidad de hábitats. Objetivo: Conocer los patrones de uso de microhábitat, sus variaciones estacionales y la posible influencia de la filogenia en un ensamble de anuros del Chaco Serrano de Argentina. Métodos: Los muestreos se realizaron en el área protegida Parque Natural Valle Fértil, Departamento Valle Fértil, San Juan, entre el 2012 y 2017. En campo, se registró el microhábitat donde se encontró cada ejemplar y se midieron variables del sitio. Además, se determinó la disponibilidad de microhábitats. Los datos se analizaron mediante el índice de selectividad de Manly. Para evaluar variaciones temporales en el uso de microhábitats se utilizaron modelos lineales generalizados (GLM). Resultados: Las especies evaluadas fueron: Rhinella arenarum arenarum, Leptodactylus latrans, Pleurodema tucumanum y Odontophrynus occidentalis. Todas las especies mostraron diferencias en las frecuencias de uso: R. a. arenarum mostró preferencias hacia los sitios rocosos y acuáticos, P. tucumanum exhibió preferencias hacia los sitios con suelo desnudo y rocas, L. latrans y O. occidentalis presentaron mayores preferencias hacia los sitios rocosos y acuáticos. Todas las especies excepto Odontophrynus exhibieron variaciones estacionales en la selección y uso de los microhábitats. Odontophrynus occidentalis presentó diferencias en las proporciones de uso entre microhábitats. Conclusiones: Este estudio muestra la plasticidad en el uso de microhábitats como un determinante importante en la distribución espacial de anuros, sin restricciones aparentes impuestas por la competencia, el espacio ni la filogenia. Cuando la actividad de las especies es coincidente, el recurso espacial puede distribuirse de manera que se reduzca el solapamiento entre especies.

Introduction: Research on spatial resource usage and partition strategies is important to understand the mechanisms of coexistence in sympatric amphibian species, even more when there are temporal variations in habitat availability. Objective: To learn about the patterns of microhabitat use, its seasonal variations and the possible influence of phylogeny on an anuran assembly of the Chaco Serrano in Argentina. Methods: Samplings were carried out in the Valle Fértil Natural Park protected area, Valle Fértil Department, San Juan, between 2012 and 2017. In the field, we recorded the microhabitat where each specimen was found, and we also measured site variables. In addition, microhabitats availability was determined. Data were analyzed using Manly's selectivity index. Generalized linear models (GLM) were used to assess temporal variations in microhabitat use. Results: The species evaluated were: Rhinella arenarum arenarum, Leptodactylus latrans, Pleurodema tucumanum and Odontophrynus occidentalis. All species showed differences in usage frequencies: R. a. arenarum showed preferences for rocky and aquatic sites, P. tucumanum showed preferences towards bare soil and rocky sites, L. latrans and O. occidentalis showed greater preferences for rocky and aquatic sites. All species but Odontophrynus exhibited seasonal variations in microhabitat selection and usage. Odontophrynusoccidentalis showed differences in usage proportions among microhabitats. Conclusions: This study shows plasticity in microhabitat usage as an important determinant of anuran spatial distribution, without apparent restrictions imposed by space competition or phylogeny. When species activity is coincident, the space resource may be distributed in a way that species overlap is reduced.

Checklist of nematode parasites of reptiles from Argentina.

A summary of the parasitic nematodes of reptiles from Argentina is presented. It is a compilation of 29 parasitological papers published between 1992 and May 2020. This review includes information about 40 species of reptiles (4 snakes, 3 turtles, 1 anfisbaenian and 32 lizards). Twenty-six nematodes species have been reported from reptiles. The present review provides data on hosts, geographical distribution and site of infection. A host/parasite list is also provided.

Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27.

Cell cycle stimulation is a major transforming mechanism of Myc oncoprotein. This is achieved through at least three concomitant mechanisms: upregulation of cyclins and Cdks, downregulation of the Cdk inhibitors p15 and p21 and the degradation of p27. The Myc-p27 antagonism has been shown to be relevant in human cancer. To be degraded, p27 must be phosphorylated at Thr-187 to be recognized by Skp2, a component of the ubiquitination complex. We previously described that Myc induces Skp2 expression. Here we show that not only Cdk2 but Cdk1 phosphorylates p27 at the Thr-187. Moreover, Myc induced p27 degradation in murine fibroblasts through Cdk1 activation, which was achieved by Myc-dependent cyclin A and B induction. In the absence of Cdk2, p27 phosphorylation at Thr-187 was mainly carried out by cyclin A2-Cdk1 and cyclin B1-Cdk1. We also show that Cdk1 inhibition was enough for the synthetic lethal interaction with Myc. This result is relevant because Cdk1 is the only Cdk strictly required for cell cycle and the reported synthetic lethal interaction between Cdk1 and Myc.

New association between Amblyomma parvitarsum (Acari: Ixodidae) and the endemic lizard Liolaemus eleodori (Iguania: Liolaemidae) in Argentina

Records of lizard parasitizing ticks in Argentina are scarce and incomplete. We recorded a new population of Liolaemus eleodori, a lizard endemic to Argentina, parasitized by the hard tick Amblyomma parvitarsum. Hence, the objective of this study is to report this new association and enhance knowledge about its parasitism on reptiles of Argentina. To do this, we researched ectoparasitic loads. We determined different ecological predictors: intensity, mean intensity and prevalence. Our results provide the first data on the parasitism of nymphal stages on this lizard. We found a tick prevalence of 91.6% and a mean intensity of 2.45. Considering sexes, mean intensity was higher in females than in males. The gular region and lower ventral abdomen were the highest parasitized anatomical regions. This new record of the host-parasite association suggests that this relationship is not accidental, with this lizard species being central to the tick's life cycle. Probably, the microhabitat of this lizard species is essential for the tick to reach high prevalence. Our study represents an important contribution and provides additional information on parasitism in lizards of Argentina.

Efecto de la estacionalidad y lluvias en la avifauna del Chaco Serrano Austral, Argentina / The effects of seasonality and precipitation in the avifauna of the Argentine Southern Chaco Serrano

ResumenEn las regiones subtropicales, las precipitaciones tienen una marcada estacionalidad. El agua de inundaciones causadas por fuertes lluvias puede tener consecuencias importantes para los ecosistemas dependientes. Por el contrario, en periodos de sequía algunas especies de la fauna se encuentran limitadas a la oferta de los recursos disponibles en el hábitat, reflejando cambios en su diversidad y distribución. Entre los vertebrados, las aves son consideradas como excelentes indicadores ecológicos y facilitan evaluar los cambios de su hábitat. Sin embargo, en el Chaco Serrano Austral argentino poco se conoce sobre la avifauna. Nosotros estudiamos (1) el estado de residencia que presentan las especies de aves en el área austral del Chaco Serrano y (2) la relación de su riqueza y abundancia con la variación estacional y con los efectos de hidroperíodos mensuales y anuales. Realizamos 18 muestreos durante un período de dos años (marzo 2011 - febrero 2013) en el sector noreste del Parque Natural Valle Fértil en la provincia de San Juan, Argentina. Estos muestreos se llevaron a cabo durante los períodos no reproductivo (otoño-invierno), pre-reproductivo (primavera) y reproductivo (verano), con el fin de evaluar el estado de residencia de las aves. En cada muestreo se registraron las poblaciones de aves utilizando cinco transectas, con el fin de registrar su abundancia y riqueza específica. Con el fin de analizar las relaciones entre las variables se utilizó un modelo lineal generalizado mixto. Se registraron 98 especies de aves (44 especies residentes, 23 visitantes que llegan en primavera, seis visitantes de verano, dos visitantes de invierno y 23 con registros escasos), pertenecientes a 33 familias. Asimismo, registramos 68 especies en ambos hidroperíodos, 28 durante el hidroperíodo de lluvia y dos durante el hidroperíodo de sequía. Tanto la riqueza, como la abundancia de aves fueron mayores en el periodo prereproductivo y durante el hidroperíodo anual lluvioso, mientras que las lluvias mensuales aisladas no presentaron esta tendencia. La avifauna registrada en este artículo es similar a la encontrada en las regiones del Chaco Serrano, que fue identificado como una región clave para la preservación de la biodiversidad. Por lo tanto, recomendamos tomar esta área como prioritaria para la conservación. Los cambios en la abundancia de aves se asociaron con la llegada de las especies migratorias, sobre todo con las visitantes estivales tempranas, y probablemente en relación con su actividad reproductiva y la evolución estacional de los recursos alimentarios. El Chaco Serrano Austral subtropical semiárido parece ser un importante lugar de cría para muchas especies migratorias que además promueven los cambios estacionales en la densidad y diversidad de especies, sobre todo en los años lluviosos. La creciente comprensión en las causas de variación de la riqueza y abundancia de aves del Chaco Serrano Austral observadas en este trabajo, contribuirán con las tareas manejo y conservación de este importante grupo faunístico.

AbstractIn subtropical regions like the Chaco Serrano (33° S), rainfall has a marked seasonality, and water flood, caused by heavy rains, may have important consequences for dependent ecosystems. Conversely, the high pressure on available resources during dry periods can also affect the fauna diversity and distribution. Even though birds have shown to be excellent ecological indicators of these shifts in the environment, currently little is known about the avifauna of the Argentine Chaco Serrano phytogeographic district. Our aim was to study the resident bird population status in the Southern Chaco Serrano, its fluctuations in richness and abundance, and its relationship to seasonal variations, in monthly and annual hydroperiods. In order to assess the resident bird status over a two year period (2011 Mar.-2013 Feb.) we carried out 18 sampling surveys during pre-breeding (spring), breeding (summer) and non breeding periods (autumn-winter), in the Northeastern part of the Valle Fértil Natural Park, San Juan province, Argentina. During each site survey, we recorded bird assemblages found in six transects, and obtained bird abundance and species diversity. A mixed general linear model was employed to evaluate relationships between the studied variables. We found a total of 98 species of birds belonging to 33 families (44 resident species, 23 spring visitors, six summer visitors, two winter visitors and 23 with scarce registers). We also registered 68 of these species in both hydroperiods, 28 only during rainy periods and only two during the dry period. Both richness and abundance showed the highest values during the pre-breeding and rainy seasons, while different tendencies were detected during the isolated monthly rainfalls. These changes in bird densities were associated with the arrival of migratory species, mainly spring visitors, and probably in relationship with their reproductive activity, and to seasonal fluctuations in food resources. The Southern Chaco Serrano is a subtropical semiarid place that seems to be an important breeding habitat for many migrant bird species, which in turn promoted seasonal changes in species density and diversity, mainly during rainy years. This work contributed to our understanding on the causes of richness and abundance variations on birds, and will contribute to this important group management and conservation in this area. Rev. Biol. Trop. 65 (3): 953-961. Epub 2017 September 01.

Descripción de los pacientes con fibrilación auricular no valvular que ingresan al servicio de urgencias / Description of patients with non-valvular atrial fibrillation admitted to the emergency room

Introducción y objetivos: La fibrilación auricular es la arritmia cardiaca más frecuente y una de las complicaciones más temidas es la embolia sistémica y/o el accidente cerebrovascular (ACV). En la actualidad se cuenta con diversas terapias antitrombóticas para prevención del primero, sin embargo, hay temor por complicaciones relacionadas con la anticoagulación, y aunque existen recomendaciones de diferentes guías de prácticas clínicas, continúa el uso subóptimo de la misma. El objetivo del estudio es describir datos clínicos, diagnósticos y terapéuticos de pacientes con fibrilación auricular que ingresan al servicio de urgencias, además, se realizó una correlación entre el riesgo de embolia sistémica y de sangrado con el tipo de terapia recibida. Métodos: Estudio descriptivo retrospectivo tipo serie de casos de pacientes con diagnóstico de la fibrilación auricular no valvular durante un año. Se reportan las frecuencias de comorbilidades, diagnósticos de ingreso y tipo de terapia específica. Resultados: Se incluyeron 98 pacientes, la media de edad fue 72 años, la falla cardiaca y la hipertensión arterial fueron las principales comorbilidades; el 92% tenían indicación de anticoagulación por la escala CHA2DS2VASc, 54% de estos pacientes no la venían recibiendo a pesar de que se calculó en la mayoría bajo riesgo de sangrado. El 5% de los pacientes ingresaron con diagnóstico de ACV isquémico y el 5% presentaban sobreanticogulación. Conclusión: Las características de nuestra población con la fibrilación auricular es similar a la descrita en la literatura, pero existe baja adherencia a las recomendaciones terapéuticas en anticoagulación.

Introduction and motivation: Atrial fibrillation is the most common cardiac arrhythmia. One of its most feared complications is the systemic embolism and/or the cerebrovascular accident (CVA) or stroke. Nowadays several antithrombotic therapies are available for the former; however, there are fears regarding complications related to anticoagulation, and even though recommendations of different clinical practice guidelines exist, blood-thinning drugs are still being underused. The goal of this study is to describe clinical, diagnostic and therapeutic data of patients admitted in the emergency room with atrial fibrillation; in addition, a correlation was made between the risk of systemic embolism and bleeding depending on the received treatment. Methods: Retrospective, descriptive study of case series of patients diagnosed with non-valvular atrial fibrillation during a year. Comorbidity frequencies, admission diagnoses and specific therapy types are reported. Results: 98 patients were included, average age was 72 years old, cardiac failure and high blood pressure were the main comorbidities; 92% showed an indication for anticoagulation therapy according to the CHA2DS2-VASc scale, 54% of those patients had not been receiving this therapy despite a low risk for bleeding was established for most of them. 5% of the patients received an admission diagnosis of ischemic stroke and 5% showed overanticoagulation. Conclusion: The characteristics of our sample with atrial fibrillation are similar to those described in the literature, but there is a low adherence to the treatment recommendations for anticoagulation therapy.

MGMT Expression Predicts PARP-Mediated Resistance to Temozolomide.

Melanoma and other solid cancers are frequently resistant to chemotherapies based on DNA alkylating agents such as dacarbazine and temozolomide. As a consequence, clinical responses are generally poor. Such resistance is partly due to the ability of cancer cells to use a variety of DNA repair enzymes to maintain cell viability. Particularly, the expression of MGMT has been linked to temozolomide resistance, but cotargeting MGMT has proven difficult due to dose-limiting toxicities. Here, we show that the MGMT-mediated resistance of cancer cells is profoundly dependent on the DNA repair enzyme PARP. Both in vitro and in vivo, we observe that MGMT-positive cancer cells strongly respond to the combination of temozolomide and PARP inhibitors (PARPi), whereas MGMT-deficient cells do not. In melanoma cells, temozolomide induced an antiproliferative senescent response, which was greatly enhanced by PARPi in MGMT-positive cells. In summary, we provide compelling evidence to suggest that the stratification of patients with cancer upon the MGMT status would enhance the success of combination treatments using temozolomide and PARPi.

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle.

Myc (c-Myc) counteracts p27 effects, and low p27 usually correlates with high Myc expression in human cancer. However there is no information on the co-expression of both genes in chronic lymphocytic leukemia (CLL). We found a lack of correlation between RNA and protein levels of p27 and Myc in CLL cells, so we determined the protein levels by immunoblot in 107 cases of CLL. We observed a high p27 protein expression in CLL compared to normal B cells. Ectopic p27 expression in a CLL-derived cell line resulted in cell death resistance. Surprisingly, Myc expression was very low or undetectable in most CLL cases analyzed, with a clear correlation between high p27 and low Myc protein levels. This was associated with low Skp2 expression, which is consistent with the Skp2 role in p27 degradation and with SKP2 being a Myc target gene. High Myc expression did not correlate with leukemia progression, despite that cell cycle-related Myc target genes were upregulated. However, biochemical analysis showed that the high p27 levels inhibited cyclin-Cdk complexes even in Myc expressing CLL cells. Our data suggest that the combination of high p27 and low Myc is a marker of CLL cells which is mediated by Skp2.

MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib.

Untreated chronic myeloid leukemia (CML) progresses from chronic phase to blastic crisis (BC). Increased genomic instability, deregulated proliferation, and loss of differentiation appear associated to BC, but the molecular alterations underlying the progression of CML are poorly characterized. MYC oncogene is frequently deregulated in human cancer, often associated with tumor progression. Genomic instability and induction of aberrant DNA replication are described as effects of MYC. In this report, we studied MYC activities in CML cell lines with conditional MYC expression with and without exposure to imatinib, the front-line drug in CML therapy. In cells with conditional MYC expression, MYC did not rescue the proliferation arrest mediated by imatinib but provoked aberrant DNA synthesis and accumulation of cells with 4C content. We studied MYC mRNA expression in 66 CML patients at different phases of the disease, and we found that MYC expression was higher in CML patients at diagnosis than control bone marrows or in patients responding to imatinib. Further, high MYC levels at diagnosis correlated with a poor response to imatinib. MYC expression did not directly correlate with BCR-ABL levels in patients treated with imatinib. Overall our study suggests that, as in other tumor models, MYC-induced aberrant DNA synthesis in CML cells is consistent with MYC overexpression in untreated CML patients and nonresponding patients and supports a role for MYC in CML progression, possibly through promotion of genomic instability.

SKP2 oncogene is a direct MYC target gene and MYC down-regulates p27(KIP1) through SKP2 in human leukemia cells.

SKP2 is the ubiquitin ligase subunit that targets p27(KIP1) (p27) for degradation. SKP2 is induced in the G(1)-S transit of the cell cycle, is frequently overexpressed in human cancer, and displays transformation activity in experimental models. Here we show that MYC induces SKP2 expression at the mRNA and protein levels in human myeloid leukemia K562 cells with conditional MYC expression. Importantly, in these systems, induction of MYC did not activate cell proliferation, ruling out SKP2 up-regulation as a consequence of cell cycle entry. MYC-dependent SKP2 expression was also detected in other cell types such as lymphoid, fibroblastic, and epithelial cell lines. MYC induced SKP2 mRNA expression in the absence of protein synthesis and activated the SKP2 promoter in luciferase reporter assays. With chromatin immunoprecipitation assays, MYC was detected bound to a region of human SKP2 gene promoter that includes E-boxes. The K562 cell line derives from human chronic myeloid leukemia. In a cohort of chronic myeloid leukemia bone marrow samples, we found a correlation between MYC and SKP2 mRNA levels. Analysis of cancer expression databases also indicated a correlation between MYC and SKP2 expression in lymphoma. Finally, MYC-induced SKP2 expression resulted in a decrease in p27 protein in K562 cells. Moreover, silencing of SKP2 abrogated the MYC-mediated down-regulation of p27. Our data show that SKP2 is a direct MYC target gene and that MYC-mediated SKP2 induction leads to reduced p27 levels. The results suggest the induction of SKP2 oncogene as a new mechanism for MYC-dependent transformation.

Gestational diabetes mellitus alters maternal and neonatal circulating endothelial progenitor cell subsets.

OBJECTIVE: The purpose of this study was to examine whether women with gestational diabetes mellitus (GDM) and their offspring have reduced endothelial progenitor cell subsets and vascular reactivity. STUDY DESIGN: Women with GDM, healthy control subjects, and their infants participated. Maternal blood and cord blood were assessed for colony-forming unit-endothelial cells and endothelial progenitor cell subsets with the use of polychromatic flow cytometry. Cord blood endothelial colony-forming cells were enumerated. Vascular reactivity was tested by laser Doppler imaging. RESULTS: Women with GDM had fewer CD34, CD133, CD45, and CD31 cells (circulating progenitor cells [CPCs]) at 24-32 weeks' gestation and 1-2 days after delivery, compared with control subjects. No differences were detected in colony-forming unit-endothelial cells or colony-forming unit-endothelial cells. In control subjects, CPCs were higher in the third trimester, compared with the postpartum period. Cord blood from GDM pregnancies had reduced CPCs. Vascular reactivity was not different between GDM and control subjects. CONCLUSION: The normal physiologic increase in CPCs during pregnancy is impaired in women with GDM, which may contribute to endothelial dysfunction and GDM-associated morbidities.

Thermal biology of Phymaturus lizards: evolutionary constraints or lack of environmental variation?

Several aspects of the biology of Phymaturus lizards including their herbivorous diet, specialized microhabitat use, and viviparous reproductive mode are highly conserved within the group. Here, we explore two aspects of Phymaturus thermal biology and test for the co-evolution among aspects of the thermal biology in these lizards, such as thermal preferenda and critical temperatures. Secondly, we explore correlations among variation in thermal biology with elevation and latitude. To do so, we used phylogenetically based comparative analyses (PCM) together with conventional statistics. Our results show that thermal biology for Phymaturus is conservative and our data do not suggest the co-evolution of thermal variables. Moreover, we detected low levels of variation in the thermal parameters studied, and no clear relationships between climatic and thermal variables. As a significant association between climatic and thermal variables could be demonstrated for a set of syntopic Liolaemus lizards, we suggest that thermal biology in Phymaturus lizards may be evolutionarily or ecologically constrained.

Inhibition of cell differentiation: a critical mechanism for MYC-mediated carcinogenesis?

Despite its early discovery and relevance in cancer, the mechanisms by which MYC brings about tumorigenic transformation have not been clarified. MYC elicits a variety of biological activities, the proliferation promotion being the best studied. However, inhibition of cell differentiation was one of the first MYC activities described. The importance of differentiation impairment in MYC-induced tumorigenesis is demonstrated in transgenic mice models with conditional MYC expression, where MYC inactivation leads to tumor regression associated to re-differentiation of tumor cells. To explain the anti-differentiation effects of MYC, it has been argued that MYC impairs differentiation by preventing exit from the cell cycle. However, we have described models where MYC blocks the erythroid or neuronal differentiation without reversing the proliferative arrest. In these and other models discussed here, MYC-mediated inhibition of differentiation occurs by blocking the upregulation of transcription factors that control the differentiation. The importance of MYC anti-differentiation function has recently gained importance after the discovery that MYC is one of the four transcription factors able to reprogram differentiated cells into pluripotent cells. We will discuss the hypothesis that MYC engages common pathways as a "stemness" keeper and as an oncogene.

A role for CXCR2 in senescence, but what about in cancer?

Senescence is an irreversible arrest triggered by stresses such as telomere shortening, DNA damage, or oncogenic signaling. Oncogene-induced senescence occurs in preneoplastic lesions, but it is absent from full-blown malignancies suggesting a tumor suppressor function. We recently found that depletion of the receptor CXCR2 [which binds to chemokines such as interleukin (IL)-8 or GROalpha] delays both replicative senescence and impairs the senescence response to oncogenic signals. Our findings suggest that signaling by IL-8 and GROalpha might limit tumor growth by reinforcing senescence early in tumorigenesis. The challenge remains in how to integrate this with the well-known tumor promoting effects of IL-8 and GROalpha.

Myc inhibits p27-induced erythroid differentiation of leukemia cells by repressing erythroid master genes without reversing p27-mediated cell cycle arrest.

Inhibition of differentiation has been proposed as an important mechanism for Myc-induced tumorigenesis, but the mechanisms involved are unclear. We have established a genetically defined differentiation model in human leukemia K562 cells by conditional expression of the cyclin-dependent kinase (Cdk) inhibitor p27 (inducible by Zn(2+)) and Myc (activatable by 4-hydroxy-tamoxifen). Induction of p27 resulted in erythroid differentiation, accompanied by Cdk inhibition and G(1) arrest. Interestingly, activation of Myc inhibited p27-mediated erythroid differentiation without affecting p27-mediated proliferation arrest. Microarray-based gene expression indicated that, in the presence of p27, Myc blocked the upregulation of several erythroid-cell-specific genes, including NFE2, JUNB, and GATA1 (transcription factors with a pivotal role in erythropoiesis). Moreover, Myc also blocked the upregulation of Mad1, a transcriptional antagonist of Myc that is able to induce erythroid differentiation. Cotransfection experiments demonstrated that Myc-mediated inhibition of differentiation is partly dependent on the repression of Mad1 and GATA1. In conclusion, this model demonstrates that Myc-mediated inhibition of differentiation depends on the regulation of a specific gene program, whereas it is independent of p27-mediated cell cycle arrest. Our results support the hypothesis that differentiation inhibition is an important Myc tumorigenic mechanism that is independent of cell proliferation.