FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells

1. Download : Download high-res image (153KB)
2. Download : Download full-size image

     

Portrait of human tapeworms

The tapeworms of the genus Taenia that infect human beings are T. solium, T. saginata and T. saginata asiatica. Taenia solium and T. saginata exhibit unequivocal features that characterize them; in contrast, only recent DNA studies, morphological characteristics, and epidemiological and sanitary aspects indicate that T. saginata asiatica is a subspecies of T. saginata. These 3 tapeworms occur in humans in their adult stage, and the intermediate hosts are pigs for T. solium and T. saginata asiatica and cows for T. saginata. Their identification is crucial considering the migratory increase from Asia to the Western Hemisphere and the fact that these tapeworms coexist in the same environment in Asia; furthermore, it is estimated that movement in both directions across the United States-Mexico border exceeds 200 million persons per yr, and thus, opportunities for acquiring and transporting T. solium infections are multiplied. It is not easy to distinguish among these tapeworms; therefore, a comparative diagram of the 3 parasites is shown in this article, which will facilitate their identification. All morphological features, some of which allow for identification, are clear and can be easily distinguished among the 3 tapeworms.     

Effect of Oxotremorine on Ornithine Decarboxylase Activity of the Adrenal Gland in Rat

Abstract: In this work we have studied the mechanism for the increase of adrenal ODC (ornithine decarboxylase, EC 4.1.1.17) activity provoked by oxotremorine, a muscarinic agonist. 1. Oxotremorine increased medullary ODC activity maximally at 2 h. Cortical enzyme responded much more slowly. 2. Blockade of peripheral muscarinic receptors with methylatropine partially reduced the response to oxotremorine in the medulla, but not cortex. 3. Hy-pophysectomy abolished the cortical, but not the medullary, responses to oxotremorine. Methylatropine reduced the effect of oxotremorine on medullary ODC in hypophysectomized rats. 4. In unilaterally splanchnicotomized rats oxotremorine caused an increase of ODC activity of the denervated adrenal gland relative to control value; activities in both medulla and cortex were significantly lower than those observed in the innervated gland. Evidence was obtained for a compensatory increase of ODC activity of the adrenal cortex (but not medulla) on the intact side of unilaterally operated rats. 5. Surgical intervention, in the form of a sham operation for transection of the spinal cord, leads to an increase of ODC activity in both parts of the adrenal gland. Transection of the cord attenuates these increases. 6. The additional increase of medullary ODC activity owing to the administration of oxotremorine to sham-operated rats is partially reduced in the adrenal medulla by muscarinic blockade, and completely in the cortex. This effect of methylatropine in regard to cortical ODC activity was not apparent in the other experiments with intact or unilaterally splanchnicotomized (unoperated side) rats. The results with unilaterally splanchnicotomized rats and those with transected spinal cord suggest that oxotremorine-induced modifications of adrenal ODC activity are centrally mediated, above the level of origin of the splanchnic nerves in the spinal cord (T_8–10). Experiments with hypophysectomized rats show that the response of the adrenal cortex to oxotremorine is entirely mediated by the hypophysis.     

Evaluation of the Impact of a Food Program on the Micronutrient Nutritional Status of Argentinean Lactating Mothers

This study was conducted to evaluate the impact of a food aid program (Plan Más Vida, PMV) on the micronutrient nutritional condition of lactating mothers 1?year after its implementation. The food program provided supplementary diets (wheat- and maize-fortified flour, rice or sugar, and fortified soup) to low-income families from the province of Buenos Aires, Argentina. A prospective, non-experimental study was carried out to evaluate the micronutrient nutritional status of lactating mothers (n?=?178 at baseline and n?=?151 after 1?year). Biochemical tests (hemoglobin, ferritin, zinc, vitamin A, and folic acid), anthropometric assessments (weight and height) and dietary surveys (24-h recall) were performed. We found no significant changes in anthropometric values 1?year after the intervention. The risk for vitamin A (retinol 20?C30???g/dl) and folate deficiency significantly decreased 1?year after PMV implementation (56.3 vs. 29.9 and 50.3 vs. 3.4?%, respectively; p?<?0.001). Anemia was seen in 25.8?% of lactating mothers at baseline, without statistically significant differences 1?year after (p?=?0.439). The nutritional data obtained after assessing the early impact of PMV actions may be useful to provincial health authorities to perform periodic evaluations in the future.     

Mapping and characterization of the primary and anamnestic H-2(d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus

Cytotoxic T lymphocytes (CTLs) are important for the control of virus replication during respiratory infections. For human metapneumovirus (hMPV), an H-2(d)-restricted CTL epitope in the M2-2 protein has been described. In this study, we screened the hMPV F, G, N, M, M2-1, and M2-2 proteins using three independent algorithms to predict H-2(d) CTL epitopes in BALB/c mice. A dominant epitope (GYIDDNQSI) in positions 81 to 89 of the antitermination factor M2-1 and a subdominant epitope (SPKAGLLSL) in N(307-315) were detected during the anti-hMPV CTL response. Passive transfer of CD8(+) T-cell lines against M2-1(81-89) and N(307-315) protected Rag1(-/-) mice against hMPV challenge. Interestingly, diversification of CTL targets to include multiple epitopes was observed after repetitive infections. A subdominant response against the previously described M2-2 epitope was detected after the third infection. An understanding of the CTL response against hMPV is important for developing preventive and therapeutic strategies against the virus.     

Determination of robustness and optimal work conditions for a purification process of a therapeutic recombinant protein using response surface methodology

A typical chromatographic purification step has numerous operating parameters that can impact its performance. As it is not feasible to evaluate the influence of each one, the current practice in biopharmaceutical industry is to apply risk analysis approach to identify process parameters that should be examined during process characterization. Once these parameters are identified, a response surface study can be run to help understand the relationship between critical inputs and outputs. We performed a study comprising optimization and robustness determination for a Blue-Sepharose purification step of rhEPO, a well-known therapeutic glycoprotein. Initially, risk analysis was fulfilled to identify key parameters. A small-scale model was created and qualified before its use in experimental studies, given by a Box-Behnken design with three factors. This method proved to be a very useful tool in bioprocess validation studies in which many input variables can affect product quality and safety.     

AMPA receptor-mediated toxicity in oligodendrocyte progenitors involves free radical generation and activation of JNK,calpain and caspase 3

The molecular mechanisms underlying AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor-mediated excitotoxicity were characterized in rat oligodendrocyte progenitor cultures. Activation of AMPA receptors, in the presence of cyclothiazide to selectively block desensitization, produced a massive Ca(2+) influx and cytotoxicity which were blocked by the antagonists CNQX and GYKI 52466. A role for free radical generation in oligodendrocyte progenitor cell death was deduced from three observations: (i) treatment with AMPA agonists decreased intracellular glutathione; (ii) depletion of intracellular glutathione with buthionine sulfoximine potentiated cell death; and (iii) the antioxidant N -acetylcysteine replenished intracellular glutathione and protected cultures from AMPA receptor-mediated toxicity. Cell death displayed some characteristics of apoptosis, including DNA fragmentation, chromatin condensation and activation of caspase-3 and c-Jun N-terminal kinase (JNK). A substrate of calpain and caspase-3, alpha-spectrin, was cleaved into characteristic products following treatment with AMPA agonists. In contrast, inhibition of either caspase-3 by DEVD-CHO or calpain by PD 150606 protected cells from excitotoxicity. Our results indicate that overactivation of AMPA receptors causes apoptosis in oligodendrocyte progenitors through mechanisms involving Ca(2+) influx, depletion of glutathione, and activation of JNK, calpain, and caspase-3.