Control of Sugar and Amino Acid Feeding via Pharyngeal Taste Neurons

Insect gustatory systems comprise multiple taste organs for detecting chemicals that signal palatable or noxious quality. Although much is known about how taste neurons sense various chemicals, many questions remain about how individual taste neurons in each taste organ control feeding. Here, we use the Drosophila pharynx as a model to investigate how taste information is encoded at the cellular level to regulate consumption of sugars and amino acids. We first generate taste-blind animals and establish a critical role for pharyngeal input in food selection. We then investigate feeding behavior of both male and female flies in which only selected classes of pharyngeal neurons are restored via binary choice feeding preference assays as well as Fly Liquid-Food Interaction Counter assays. We find instances of integration as well as redundancy in how pharyngeal neurons control behavioral responses to sugars and amino acids. Additionally, we find that pharyngeal neurons drive sugar feeding preference based on sweet taste but not on nutritional value. Finally, we demonstrate functional specialization of pharyngeal and external neurons using optogenetic activation. Overall, our genetic taste neuron protection system in a taste-blind background provides a powerful approach to elucidate principles of pharyngeal taste coding and demonstrates functional overlap and subdivision among taste neurons.SIGNIFICANCE STATEMENT Dietary intake of nutritious chemicals such as sugars and amino acids is essential for the survival of an animal. In insects, distinct classes of taste neurons control acceptance or rejection of food sources. Here, we develop a genetic system to investigate how individual taste neurons in the Drosophila pharynx encode specific tastants, focusing on sugars and amino acids. By examining flies in which only a single class of taste neurons is active, we find evidence for functional overlap as well as redundancy in responses to sugars and amino acids. We also uncover a functional subdivision between pharyngeal and external neurons in driving feeding responses. Overall, we find that different pharyngeal neurons act together to control intake of the two categories of appetitive tastants.     

Stabilization of glomerular filtration rate in advanced chronic kidney disease: a two-year follow-up of a cohort of chronic kidney disease patients stages 4 and 5

This study examines whether stabilization of the glomerular filtration rate (GFR) is possible in patients with advanced chronic kidney disease (CKD), managed in a CKD clinic. A cohort of 82 patients with stages 4 and 5 CKD was followed for a period of 2 years after initiation of erythropoietin for anemia to determine the GFR and the frequency of primary outcomes (dialysis, transplantation, or death). GFR, calculated by the abbreviated Modification of Diet in Renal Disease formula, was determined every 3 months. After 24 months, 35 subjects (43%) developed a primary outcome. Controlled for other risk factors, the risk of having a primary outcome increased 19.7% for every unit that the GFR decreased (95% confidence interval [CI], 11.9%-26.8%, P < .001) and decreased 21.7% for every unit that the hemoglobin increased (95% CI, 0.5%-38.4%, P < .001). Blacks had a 3.1 times higher risk (95% CI, 1.4-6.9, P = .006) of developing a primary outcome than other ethnicities. In subjects who did not develop primary outcomes (n = 47 or 57%), GFR remained unchanged (19.5 +/- 9.1 at the end of the study v 20.8 +/- 5.3 mL/min/1.73 m(2) at baseline, P = .16). The standardized mortality rate was 4.75 and 9.77 per 100 person-year for stages 4 and 5, respectively. We conclude that stabilization of GFR over a 2-year period can be achieved in many patients with advanced CKD treated with erythropoietin in a CKD clinic. Although the precise reason for the stabilization of GFR cannot be elucidated from this study, our data are "proof of concept" that CKD outcomes can be improved in a CKD clinic setting.     

Haploinsufficiency of the cdc2l gene contributes to skin cancer development in mice

The Cdc2L gene encodes for the cyclin-dependent kinase 11 (CDK11) protein. Loss of one allele of Cdc2L and reduced CDK11 expression has been observed in several cancers, implicating its association with carcinogenesis. To directly investigate the role of CDK11 in carcinogenesis, we first generated cdc2l haploinsufficient mice by gene trap technology and then studied the susceptibility of these gene-trapped (cdc2l(GT)) mice to chemical-mediated skin carcinogenesis in the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis model. Wild-type and cdc2l(GT) mice were subjected to a single topical application of initiation by DMBA and promotion twice a week for 19 weeks with TPA. At 19 weeks, 70% of the cdc2l(GT) mice and 60% of the cdc2l+/+ mice developed benign papillomas. However, there was an overall 3-fold increase in the average number of tumors per mouse observed in cdc2l(GT) mice as compared with cdc2l+/+ mice. There was also an increased frequency of larger papillomas in cdc2l(GT) mice. By using the polymerase chain reaction-restriction fragment length polymorphism assay, we found A to T transversion mutations at the 61st codon of H-ras gene in the papilloma tissue of both cdc2l(GT) mice and cdc2l+/+ mice. Ki-67 staining revealed increased proliferation in the papillomas of cdc2l(GT) (77.75%) as compared with cdc2l+/+ (30.84%) tumors. These studies are the first to show that loss of one allele of cdc2l gene, encoding CDK11, facilitates DMBA/TPA-induced skin carcinogenesis in vivo.     

Large pulmonary cryptococcoma and cryptococcal meningitis in an immunocompetent patient: A case report

Pulmonary cryptococcoma is a life threatening mycosis and is an unusual disease for immunocompetent individuals. Herein we report a case of large pulmonary cryptococcoma associated with cryptococcal meningitis, presenting radiologically as a lung mass in right upper lobe, in a previously healthy, HIV negative, immunocompetent young individual. Since cryptococcosis continues to be an important infection in HIV negative patients and is associated with substantial overall and cause‐specific mortality, the need for consideration of this entity in the differential diagnosis of a lung mass is emphasized. Diagn. Cytopathol. 2010;38:929–931. © 2010 Wiley‐Liss, Inc.     

Gender and status asthmaticus.

BACKGROUND: Adult women may be more susceptible to asthma than men. HYPOTHESIS: Women are more likely to develop status asthmaticus (SA) requiring critical care. METHODS: The medical records of patients admitted to our medical intensive care unit (ICU) for SA between 1994 and 2000 were examined. A number of demographic and physiologic variables were extracted from the medical records. RESULTS: Of 103 total admissions, 53 (of 37 patients) were age < 50 years and had clinical evidence suggesting SA. Among these 37 patients, the average (+/-SE) age was 30.8 +/- 1.0 y with average acute physiology and chronic health evaluation (APACHE) II of 9.5 +/- 0.8. Seventeen patients were Hispanic, 13 were black, and 7 were white. Twenty-four patients (accounting for 37 admissions) were female and 13 patients (16 admissions) were male. Although women accounted for a greater absolute number of endotracheal intubations (ETI; 17 vs. 12) and were more likely to be admitted to ICU more than once (7 vs. 3), men had a higher incidence of ETI (RR=1.6; 95%CI=1.04-2.6). The need for using therapeutic permissive hypercapnia and lengths of stay (ventilator, ICU, and hospital) were similar between men and women. Two patients, both women, died of causes not related to treatment of SA. CONCLUSIONS: These data suggest that although women accounted for more ICU admissions for SA, men were more likely to require ETI.     

Histogenesis of uterus in human fetuses

Introduction

The histological changes during the development of the human uterus throughout the fetal period exhibit varying cellular patterns in the lining epithelium. The present study documents these progressive changes during fetal uterine maturation.

Effect of olsalazine on sodium-dependent bile acid transport in rat ileum

Olsalazine (OLZ), a relatively new form of 5-aminosalicylic acid (5-ASA), is being used for the treatment of colitis. A major side effect of olsalazine is diarrhea, reported in 12–25% of patients. One suggested mechanism for this side effect is enhanced ileal water and electolyte secretion. We propose that OLZ may also inhibit ileal bile acid (BA) transport, resulting in choleretic diarrhea. This would result in excess BAs reaching the colon, with consequent BA-induced secretory diarrhea. Therefore, we studied the effect of OLZ on rat ileal absorption of taurocholate. BA uptake was determined in rat ileal segments, everted sacs, brush border membrane vesicles (BBMV), andXenopus laevis oocytes. Segments and everted sacs were treated with 5 mM OLZ for 30 min prior to and throughout 10-min taurocholate (Tc) uptake. Terminal ileal BBMV were used to study the effect of OLZ on sodium-dependent bile acid uptake independent of cellular metabolism. Direct effects on the bile acid carrier were examined usingXenopus laevis oocytes expressing the cloned apical rat ileal BA transporter. In ileal segments 5 mM OLZ inhibited 10-min Tc uptake by 69.4±8.8% (P<0.01) (N=10 animals). Increasing concentrations of OLZ resulted in a dose-dependent inhibition of Tc uptake. Ten-minute Tc uptake with 0.5, 1.0, 2.0, 2.5, and 5 mM OLZ was inhibited by 13.5, 39.6, 49.7, and 70.5%, respectively. In BBMV, OLZ inhibited 45-sec Tc uptake in a dose-dependent manner but did not effect Na-dependentl-alanine uptake. Kinetic analysis revealed a noncompetitive inhibition by 2 mM olsalazine. Olsalazine, 5 mM, also inhibited Na-dependent uptake of Tc into oocytes, which expressed the rat ileal sodium-dependent bile acid transporter (8.0±3.7 vs 2.6±2.0 pmol/oocyte/hr,P<0.001). OLZ inhibits sodium-dependent Tc uptake and transmucosal transport in the rat ileum in a dose-dependent manner. This inhibition is relatively specific, noncompetitive, and does not require intact cellular mechanisms. This effect of OLZ on ileal function may contribute to the diarrhea frequently observed with this drug.Supported in part by a grant from Reach Out For Youth with IBD and a gift from Ruth & Leonard Litwin and by grants from the National Institute of Health (DK02076,34989,43509, HD07388, HD20632 and HD27757).This work was presented in part at the American Gastroenterological Association meeting, Boston, Massachusetts, May 19, 1993.Address for reprint requests: Dr. Anupama Chawla, Pediatric Gastroenterology, North Shore University Hospital-Cornell University Medical College, 300 Community Drive, Manhasset, New York 11030.     

Effect of Residual Dental Pulp Tissue on Regeneration of Dentin-pulp Complex: An In Vivo Investigation

Introduction

Current pulp revascularization procedures in teeth with necrotic pulps and open apices have produced histologic evidence of connective tissue growth, cementum, and bone within the root canals of experimental animals. This study aims to investigate the effect of maintaining uninflamed residual apical pulp tissue on the histologic outcome of pulp-dentin complex regeneration after a revascularization procedure in immature ferret cuspid teeth.