Retention deficit for avoidance training in hypophysectomized rats: Time-dependent enhancement of retention performance with post-training ACTH injections

These experiments examined the effects of hypophysectomy on retention of avoidance training. In addition, the experiments examined the effects, on retention, of post-training ACTH injections administered to hypophysectomized rats. Rats were trained in a visual discriminated avoidance Y maze. Each rat received six training trials followed by six retraining trials the next day. Retention was measured by the number of correct choices during the retraining trials. When trained with a low-footshock intensity (0.8 mA), hypophysectomized rats showed retention performance which was significantly poorer than that of intact animals. There was no significant difference in performance when the animals were trained with a higher footshock intensity (1.4 mA), in part because of poorer retention performance of intact animals under these training conditions. Under both footshock conditions, a single post-training injection of ACTH enhanced later retention performance of hypophysectomized rats. This effect on memory was timedependent; injections delayed 2 or 6 hr after training did not significantly enhance retention. These findings are consistent with the view that hormonal responses to training may modulate later retention of the training experience.     

ANAL CARCINOMA

Carcinoma of the anus is a rare tumor when skin tumors which may have arisen from the perianal skin are excluded. A significant proportion of anal carcinomas, exclusive of those from perianal skin, may very well have their origin from the intermediate zone of transitional epithelium and its and ducts, which would account for the different histological patterns presented by these cancers. These tumors are frequently described as of low grade malignancy and indeed some of them may be; but, the majority behave as very aggressive carcinomas, capable not only of rapid and extensive local invasion but also capable of lymph node metastasis. The treatment should be surgical and aggressive if operation is feasible.     

Calcium imaging reveals a network of intrinsically light-sensitive inner-retinal neurons

BACKGROUND: Mice lacking rod and cone photoreceptors (rd/rd cl) are still able to regulate a range of responses to light, including circadian photoentrainment, the pupillary light reflex, and suppression of pineal melatonin by light. These data are consistent with the presence of a novel inner-retinal photoreceptor mediating non-image-forming irradiance detection. RESULTS: We have examined the nature and extent of intrinsic light sensitivity in rd/rd cl retinae by monitoring the effect of light stimulation (470 nm) on intracellular Ca(2+) via FURA-2 imaging. Using this approach, which does not rely on pharmacological or surgical isolation of ganglion cells from the rod and cone photoreceptors, we identified a population of light-sensitive neurons in the ganglion cell layer (GCL). Retinal illumination induced an increase of intracellular Ca(2+) in approximately 2.7% of the neurons. The light-evoked Ca(2+) fluxes were dependent on the intensity and duration of the light stimulus. The light-responsive units formed an extensive network that could be uncoupled by application of the gap junction blocker carbenoxolone. Three types of light-evoked Ca(2+) influx were observed: sustained, transient, and repetitive, which are suggestive of distinct functional classes of GCL photoreceptors. CONCLUSIONS: Collectively, our data reveal a heterogeneous syncytium of intrinsically photosensitive neurons in the GCL coupled to a secondary population of light-driven cells, in the absence of rod and cone inputs.     

Δ′-Pyrroline: An intermediary metabolite in the conversion of putrescine to 2-pyrrolidone

Δ′-Pyrroline, an oxidative product of putrescine metabolism, was chemically synthesized and incubated with a rat liver homogenate. The incubation mixture was fractionated on an amino acid analyzer before and after acid hydrolysis. The hydrolyzed sample, in contrast to the unhydrolyzed sample, contained a ninhydrin positive compound that cochromatographed with γ-aminobutyric acid, the product of 2-pyrrolidone acid hydrolysis. Authentic 2-pyrrolidone had the same retention time as the Δ′-pyrroline metabolite when analyzed by high-pressure liquid chromatography. It is concluded that Δ′-pyrroline is an intermediary metabolite in the pathway from putrescine to 5-hydroxy-2-pyrrolidone.     

Unfolded Protein Response Is Required for the Definitive Endodermal Specification of Mouse Embryonic Stem Cells via Smad2 and β-Catenin Signaling

Tremendous efforts have been made to elucidate the molecular mechanisms that control the specification of definitive endoderm cell fate in gene knockout mouse models and ES cell (ESC) differentiation models. However, the impact of the unfolded protein response (UPR), because of the stress of the endoplasmic reticulum on endodermal specification, is not well addressed. We employed UPR-inducing agents, thapsigargin and tunicamycin, in vitro to induce endodermal differentiation of mouse ESCs. Apart from the endodermal specification of ESCs, Western blotting demonstrated the enhanced phosphorylation of Smad2 and nuclear translocation of β-catenin in ESC-derived cells. The inclusion of the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid to the induction cultures prevented the differentiation of ESCs into definitive endodermal cells even when Activin A was supplemented. Also, the addition of the TGF-β inhibitor SB431542 and the Wnt/β-catenin antagonist IWP-2 negated the endodermal differentiation of ESCs mediated by thapsigargin and tunicamycin. These data suggest that the activation of the UPR appears to orchestrate the induction of the definitive endodermal cell fate of ESCs via both the Smad2 and β-catenin signaling pathways. The prospective regulatory machinery may be helpful for directing ESCs to differentiate into definitive endodermal cells for cellular therapy in the future.     

Prevalence of Vitamin D Deficiency in Sickle Cell Disease: A Systematic Review

Vitamin D deficiency has emerged as a public health focus in recent years and patients with sickle cell disease (SCD) reportedly have a high prevalence of the condition. Our objectives were to summarize definitions of vitamin D deficiency and insufficiency used in the literature, and to determine the prevalence and magnitude of each in patients with SCD through a systematic review conducted according to PRISMA guidelines. From a PubMed search, 34 potential articles were identified and 15 met eligibility criteria for inclusion. Definitions of deficiency and insufficiency varied greatly across studies making direct comparisons difficult. This review provides evidence to suggest that suboptimal vitamin D levels are highly prevalent among those with SCD, far more so than in comparable non-SCD patients or matched control populations. Defining deficiency as vitamin D <20ng/mL, prevalence estimates in SCD populations range from 56.4% to 96.4%. When compared with results from the population-based National Health and Nutrition Examination Survey, however, the general African American population appeared to have a similarly high prevalence of vitamin D deficiency. African American patients with and without SCD were both substantially higher than that of Caucasians. What remains to be determined is whether there are adverse health effects for patients with SCD because of concurrent vitamin D deficiency.     

Folic acid utilisation related to sulfa drug resistance in Saccharomyces cerevisiae

Saccharomyces cerevisiae mutants deficient in folate synthesis have been constructed and employed to study the utilisation of exogenous folates in yeast. One mutant specifically lacked dihydropteroate synthase while the second lacked dihydrofolate synthase. Exogenous folinic acid restored optimal growth to both strains. Folic acid did not generally rescue growth but spontaneous isolates capable of utilising folic acid were selected. The folic acid synthesis pathway in the folate utilising isolates was restored via transformation with FOL1 or FOL3 expression plasmids and transformants were tested for resistance to sulfamethoxazole (SMX). The presence of elevated levels of folic acid led to greatly reduced SMX sensitivity regardless of whether strains were folate utilisers or not.     

The Lectins of Sophora japonica: II. Purification, Properties, and N-Terminal Amino Acid Sequences of Five Lectins from Bark

Five N-acetyl-galactosamine-specific lectins were isolated from the bark of the legume tree Sophora japonica. These lectins are immunologically and structurally very similar, but not identical, to the Sophora seed and leaf lectins. The carbohydrate specificities and hemagglutinin activities of these lectins are indistinguishable at pH 8.5 but their activities differ markedly at pH values below 8. All five lectins are tetrameric glycoproteins made up of different combinations of subunits of about 30,000, 30,100, 33,000 M_r containing 3% to 5% covalently attached sugar. These lectins are the overwhelmingly dominant proteins in bark, but they do not appear to be present in other tissues. Amino terminal sequence analysis indicates that at least two distinct lectin genes are expressed in bark.