The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia

Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKTmutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1- activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors

Displacement electrophoresis

The method of displacement electrophoresis is described and its analogy with displacement chromatog. shown. The app. consists basically of a capillary tube, a few tenths of a mm bore and thin walled, uniting 2 vessels, each contg. an electrode. For the anal. of anions the cathode vessel contains an anion less mobile than any in the sample mixt. to be analyzed. The capillary tube is filled with a soln. of a salt of an anion more mobile than any in the sample and a buffering cation. The anode vessel contains the buffering cation. The electrodes must not produce interfering ions or gas. To reduce disturbance by electroendosmosis a long chain soluble polymer is used to increase the viscosity of the soln. in the capillary tube, and the electrode vessel is closed at the end to which electroendosmosis would cause flow if it were open. The sample is introduced between the cathode and the capillary, and a const. current is passed between the electrodes. The anions in the sample move initially at different speeds until they are sepd. in order of their mobility. Then all the anions in the app. move down the capillary at the same speed, assuming the tube to be of const. bore. The boundary between each successive pair of ions is more or less sharp, depending upon the diffusion consts., the potential gradient, the difference in mobility, and the disturbance caused by electroendosmosis, temp. difference across the capillary, and flow of liq. Each zone has a characteristic pH. Once the train of anions has sepd. it proceeds down the capillary unchanged. Since each zone has a particular potential gradient, it has also a particular rate of heat generation per unit length and a particular temp. It is thus possible to follow the sepn. by means of fixed thermocouples on the outside of the tube, which will record the fronts as they pass under the thermocouple. A thermocouple measuring the temp. of the capillary relative to its surrounding plots a series of steps on a recorder, the height of a step from the baseline being a measure of the mobility. The length of the step is preferably measured from the distance between the peaks of the record provided by a differential thermocouple measuring the difference in temp. along a short length of the tube, which gives a record which is the differential of the step curve. The length of step is proportional to the length of tube occupied by that species of ion and hence to the quantity. A qual. and quant. anal. is possible. [on SciFinder (R)

Displacement electrophoresis

The displacement method of electrophoresis has been studied for strong anions, electropherograms being given as integral and/or differential temperature recordings. The theory and utility of the method are discussed

Polyesteramide macromolecule and composition comprising such a macromolecule

The present invention relates to branched non dendrimeric macromolecules, that may be prepared from the an addition product of an a, -olefinically unsaturated compound and an amine comprising at least two hydroxyl groups; at least part of the hydroxyl groups of which are esterified with an olefinically unsaturated carboxylic acid, an olefinically unsaturated carboxylate anion oran olefin­ ically unsaturated carboxylic acid anhydride, to form the non dendrimeric macromolecule which comprises at least one amide group.<br/

Acesso ao alimento artificial e enchimento do trato digestivo de juvenis do camarão marinho Litopenaeus vannamei (Boone) (Crustacea, Decapoda, Penaeidae) durante as fases clara e escura do período de 24 horas Artificial food access and digestive tract filling of juvenil marine shrimp Litopenaeus vannamei (Boone) (Crustacea, Decapoda, Penaeidae) during light and dark phases in 24-hour period

A escassez de dados acerca do comportamento alimentar do camarão marinho Litopenaeus vannamei (Boone, 1931) com relação ao alimento artificial ofertado em bandejas poderá induzir a uma alimentação inadequada, resultando no desperdício da ração, no aporte desnecessário de nutrientes, e conseqüente aumento dos custos com a alimentação e da poluição ambiental potencial desta atividade. Objetivando fornecer subsídios para a melhoria do manejo alimentar praticado nas fazendas, foram realizados estudos comportamentais utilizando 64 juvenis de Litopenaeus vannamei (7,57 ± 1,01g), mantidos em densidade populacional de 33 m², submetidos a fotoperíodo artificial, em ciclo invertido, para observação durante as fases clara e escura. A ração foi ofertada em intervalos pré-estabelecidos, registrando-se posteriormente através de método focal contínuo: a) latência para chegada à bandeja, b) latência para consumo do alimento e c) Índice de Enchimento do Trato Digestivo. Os animais foram mais rápidos para chegar à bandeja e também para iniciar o consumo do alimento nos horários da fase clara. O enchimento do trato digestivo mostrou-se superior na meia hora subsequente à oferta do alimento, especialmente nos horários da fase clara.<br>The few data on the marine shrimp Litopenaeus vannamei (Boone, 1931) behavior related to feed offer in trays can result inadequate feeding by the animal, feed wastage and unnecessary nutrient input, increasing feed costs and potential environmental pollution of that culture. In order to provide tools for improved feed management methods in shrimp farms, a behavioral study was conducted, using 64 Litopenaeus vannamei juveniles (7,57 ± 1,01g), one animal per 33 m². They were submitted to artificial photoperiods, half of them in reversed cycle, in order to register behavior during light and dark phases. The following variables were registered (continuous sampling) after feed exposition: a) latency to access the feeding tray, b) latency to start eating and c) digestive tract filling. The animals accessed the feeding trays and started consumption faster in the light phase hours. The digestive tract filling was higher half hour following feed offer, specially in the hours during the light phase