Multiple forms of acetylcholinesterase from rat erythrocytes. Effect of fat-free diet.

Electrophoretic patterns of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) from rat erythrocyte were studied. The enzyme was solubilized by the following treatments: a) Triton X-100, b) sodium deoxycholate, or c) ultrasonic irradiation. When the erythrocyte membrane was solubilized by Triton X-100 at concentrations higher than 0.3%, by 10 mM sodium deoxycholate, or by ultrasonic irradiation for more than 5 min, a single band of acetylcholinesterase activity appeared in the gel. Two bands of activity were stained in the gel when the membrane was solubilized by Triton X-100 at concentrations between 0.1--0.2%, or by ultrasound for 5 min. Electrophoretic patterns of acetylcholinesterase from rats fed a fat-sufficient diet were similar to those for the enzyme from animals fed a fat-free diet. The recombination of lipids with the enzyme eluted from the gels confirmed the "phenotypic allosteric desensitization phenomenon".     

XY gonadal dysgenesis with female phenotype (author's transpl)]

In this paper, we are dealing with the study of a case of multiple somatic malformations, with external female genitals and 46 XY caryotype. The anatomical and histological study of the genital organs, allows us to verify the existence of internal genital organs; consisting essentially in tubes, bicornous uterus, a gonadal ligament in a normotopical position, Wolffian remains and the absence of a vagina. The external female genitals are completely normal. When we interpreted these findings, we paid special attention to the relation existing between the abnormal presence of the Wolffian remains, male genotype, and typical female genital structures. Taking account of the latest scientific advances concerning genital development, we considered the possibility of the existence of secretions of a "masculinizing" substance from the gonad, before its morphological differentiation, which was interrupted by an etiological undetermined noxa. When this evolution was arrested, together with the secretions of the masculinizing substance, the genital development continued normally for a female. The terminal teratogenic period for this malformation is situated from the 5th to the 6th week of gestation (human embryos from 11 to 14 mm., Streeter Horizon XVII).     

Melatonin in the seasonal response of the aphid Acyrthosiphon pisum

Aphids display life cycles largely determined by the photoperiod.During the warm long-day seasons.most aphid species reproduce by viviparous parthenogenesis.The shortening of the photoperiod in autumn induces a switch to sexual reproduction.Males and sexual females mate to produce overwintering resistant eggs.In addition to this full life cycle(holocycle),there are anholocyelic lineages that do not respond to changes in photoperiod and reproduce continuously by parthenogenesis.The molecular or hormonal events that trigger the scasonal response(i.c,induction of the sexual phenotypes)are still unknown.Although circadian synthesis of melatonin is known to play a key role in vertebrate photoperiodism,the involvement of the circadian clock and/or of the hor-mone melatonin in insect seasonal responses is not so well established.Here we show that melatonin levels in the aphid Acyrthosiphon pisum are significantly higher in holocyclice aphids reared under short days than under long days,while no differences were found between anholoeyelic aphids under the same conditions.We also found that melatonin is localized in the aphid suboesophageal ganglion(SOG)and in the thoracic ganglionic mass(TGM).In analogy to vertcbrates,insect-type arylalkxylamine N-acetyltransferases(i-AANATs)are thought to play a key role in melatonin synthesis.We measured the expression of four I-AANAT genes identified in A.pisum and localized two of them in situ in the insect central nervous systems(CNS).Levels of expression of these genes were compatible with the quantities of melatonin observed.Moreover,like melatonin,expression of these genes was found in the SOG and the TGM.     

Body proportions,microhabitat selection,and adaptive radiation of Liolaemus lizards in central Chile

Summary A biometric analysis of body proportions with presumably functional meaning for microhabitat selection was made on 12 species of Liolaemus lizards in central Chile. Characters studied were forelimb length, hindlimb length, tail length (all standardized by the corresponding snout-vent length), and the ratio forelimb/hindlimb length. It is shown that irrespective of terrestrial, saxicolous, or arboreal habits, Liolaemus species are remarkably similar in body proportions. The only exceptions are: L. lemniscatus, an open ground-dweller which exhibits significantly shorter limbs; and L. chiliensis and L. schroederi, both shrub-climbers which exhibit significantly longer tail. It is concluded that the adaptive radiation of Liolaemus lizards in central Chile has been accomplished mainly by diversification of activity time, food size, and microhabitat type. Morphological divergence in body proportions seems to have played an unimportant role.     

Effect of norepinephrine and vasopressin on renal kallikrein excretion in rats

The purpose of this study was to investigate the effect of norepinephrine and vasopressin on urinary kallikrein excretion in the rat. Two studies were undertaken: (a) acute experiments in which the rats were infused with 30% dextrose in water with the addition of norepinephrine or vasopressin, (b) chronic experiments in which the drugs were infused during seven days through an osmotic minipump. In acute experiments, urinary kallikrein excretion increased without modification in urinary flow and glomerular filtration rate. In chronic experiments, urinary kallikrein excretion was not modified in norepinephrine-treated rats and decreased in vasopressin-infused animals. This decrease followed the modifications of the urine flow. In chronic experiments the dextrose infusion increased urinary kallikrein excretion. In all the groups studied a positive correlation between urine flow and urinary kallikrein excretion was observed. It is concluded that norepinephrine and vasopressin are important stimulators of the urinary kallikrein excretion only in those circumstances where it is necessary to eliminate an excess of water.     

Circulating adiposity-related microRNAs as predictors of the response to a low-fat diet in subjects with obesity

Recent studies have revealed the critical role of several microRNAs (miRNAs) in energy homeostasis and metabolic processes and suggest that circulating miRNAs can be used as early predictors of weight loss in the design of precision nutrition. Thus, the aim of this study was to investigate circulating adiposity-related miRNAs as biomarkers of the response to two specific weight loss dietary treatments. The expression of 86 miRNAs was investigated in plasma of 78 subjects with obesity randomized to two different diets [moderately high-protein diet (n = 38) and low-fat diet (n = 40)] and in 25 eutrophic controls (BMI ≤ 25 kg/m²). Bioinformatic analyses were performed to explore the target genes and biological pathways regulated by the dysregulated miRNAs. As results, 26 miRNAs were found differently expressed in eutrophic and volunteers with obesity. Moreover, 7 miRNAs (miR-130a-3p, miR-142-5p, miR-144-5p, miR-15a-5p, miR-22-3p, miR-221-3p and miR-29c-3p) were differentially expressed between responders and non-responders to a low-fat diet. Furthermore, after adjustment for basal glucose levels, 1-SD increase in miR-22-3p expression was associated with reduction in the risk of non-response to low-fat diet [OR = 0.181, 95% CI (0.084-0.947), P = .043]. Bioinformatic analyses evidenced that these 7 miRNAs regulate the expression of genes participating in important metabolic pathways. Conclusively, 7 circulating miRNAs related to adiposity could be used for predicting the response to a low-fat diet intervention prescribed to lose weight.     

Pharmacological screening and transcriptomic functional analyses identify a synergistic interaction between dasatinib and olaparib in triple-negative breast cancer

Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening.