Regulated Intron Removal Integrates Motivational State and Experience.

Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.

A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates.

UNLABELLED: In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. INTRODUCTION: This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post-menopausal women with osteoporosis. METHODS: This randomized, active and placebo-controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for ≥12 months preceding the trial and any oral bisphosphonate for ≥3 of the preceding 4 years and had spine or hip BMD T-scores ≤-2.5 or ≤-1.5 with ≥1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo. RESULTS: Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P < 0.05 vs ALN). There was also a dose-dependent increase in the incidence of hypercalcemia with MK-5442. CONCLUSION: Switching from ALN to MK-5442 resulted in a pulsatile increase in PTH and increases in BTMs, but a decline in BMD compared with continued ALN. MK-5442 is not a viable option for the treatment of osteoporosis.

Translational Control by Prion-like Proteins.

Prion-like proteins overlap with intrinsically disordered and low-complexity sequence families. These proteins are widespread, especially among mRNA-binding proteins. A salient feature of these proteins is the ability to form protein assemblies with distinct biophysical and functional properties. While prion-like proteins are involved in myriad of cellular processes, we propose potential roles for protein assemblies in regulated protein synthesis. Since proteins are the ultimate functional output of gene expression, when, where, and how much of a particular protein is made dictates the functional state of a cell. Recent finding suggests that the prion-like proteins offer unique advantages in translation regulation and also raises questions regarding formation and regulation of protein assemblies.

Safety, Efficacy, and Cost-Analysis of Percutaneous Endoscopic Gastrostomy and Ventriculoperitoneal Shunt Placement in a Simultaneous Surgery.

BACKGROUND: Limited historical data suggest that concomitant placement of both a ventriculoperitoneal (VP) shunt and percutaneous endoscopic gastrostomy (PEG) tube is associated with an increased risk of complications, including VP shunt infections. Here we compare the outcomes and cost difference between 2 groups of patients, one in which a VP shunt and PEG tube were placed in the same operation and the other in which separate operations were performed. METHODS: A total of 10 patients underwent simultaneous placement of a VP shunt and PEG tube. This group was compared with a group of 18 patients that underwent separate placements. Hospital billing charges were used to compare the total cost of the procedures in the 2 groups. RESULTS: Eight of the 10 patients presented with aneurysmal subarachnoid hemorrhage. The average length of stay was 25 ± 2 days for the simultaneous procedure group and 43 ± 7 days for the separate procedures group. The average duration of follow-up was 12 ± 3 months after simultaneous placement. No patient in the simultaneous surgery group had signs of infection or shunt malfunction at last follow-up. The overall complication rate was significantly lower in the simultaneous surgery group. A cost analysis demonstrated significant cost savings by completing both procedures in the same surgical procedure. CONCLUSIONS: Simultaneous placement of a PEG tube and VP shunt is safe, efficacious, and cost-effective. Thus, in patients requiring both a VP shunt and PEG tube, placement of both devices in a single surgical procedure should be considered.

Nitric oxide synthase interneurons in the monkey cerebral cortex are subsets of the somatostatin, neuropeptide Y, and calbindin cells.

99%) immunoreactive for somatostatin and neuropeptide Y, but did not express calbindin. The LNOS cells comprised about 30% of the somatostatin cells and about 60% of the neuropeptide Y cells. The SNOS cells were nearly always (87-98%) calbindin-immunoreactive, and were rarely or never labeled with antibodies to somatostatin or neuropeptide Y. The SNOS cells accounted for about 20% of all of the calbindin cells. The findings demonstrate that the two types of nNOS cells can be distinguished by antibodies to calbindin, somatostatin and neuropeptide Y, but none of these markers is found exclusively in nNOS cells. Nevertheless, neuropeptide Y-immunoreactivity provides a useful marker for LNOS cells, because it is very dense in these cells and only light in the interneurons that lack nNOS.

Amalgam tattoo: report of an unusual clinical presentation and the use of energy dispersive X-ray analysis as an aid to diagnosis.

An unusual appearing gingival amalgam pigmentation (amalgam tattoo) that completely surrounded the maxillary right first premolar in a 13-year-old boy is presented. Because of the wide distribution and apparent clinical progression of the discoloration, an excisional biopsy was performed. The histopathologic diagnosis of amalgam pigmentation was confirmed in paraffin sections by energy dispersive X-ray microanalysis. Silver, tin, and mercury were detected in the specimen.

Tooth root growth impairment after mantle radiation in long-term survivors of Hodgkin's disease.

The tooth root growth impairment that resulted from 35 to 37 Gy mantle port radiation in 47 long-term survivors of childhood Hodgkin's disease was quantified and related to specific age groups and categories of teeth. Root measurements of the mandibular permanent canines, first and second premolars, and first and second molars were made from sequential panoramic radiographs taken at the time of radiation therapy and after the closure of root apexes. The severity of root growth impairment was greatest in patients who received radiation during the early stages of odontogenesis. With later stages of odontogenesis, and as the age increased at the time of treatment, less impairment occurred. The potential difficulties of using repeated panoramic radiographs to assess tooth lengths in longitudinal studies also were discussed.

Influence of sodium pentobarbital on pH, sarcomere length, and muscle tenderness of broiler Pectoralis major muscle.

Six trials were conducted to determine the effect of sodium pentobarbital (SP) anesthesia on broiler muscle pH, sarcomere length, and Allo-Kramer shear values. Birds were divided into six groups, three of which were anesthetized with SP prior to slaughter. Birds from both the anesthetized and nonanesthetized groups were subjected to one of three processing treatments: 1) muscles hot boned as soon as possible after death and immediately analyzed (HB/0); 2) muscles hot boned and aged 24 h in ice/water slush (HB/24); and 3) muscles left on carcass (conventional process) and aged 24 h in ice/water slush (CP/24) before deboning. The SP/HB/0 group was found to have significantly higher (P less than .05) pH values and longer sarcomere lengths than those of the other five treatment groups. No significant differences were observed for pH among the four 24-h aged groups. Sarcomere lengths were found to be shortest in the SP/HB/24 and HB/24 groups followed by SP/CP/24, HB/0, and CP/24 groups. The CP/24 and SP/CP/24 groups had the lowest shear values, with the HB/0, HB/24, and SP/HB/24 groups exhibiting three-fold higher shear values. These results indicate that SP can delay the effects of ante-mortem stress on early rigor processes; however, no such effects were apparent following 24-h aging.

Early post-mortem metabolism and muscle shortening in the Pectoralis major muscle of broiler chickens.

Three experiments were conducted to examine the effects of sodium pentobarbital (SP), iodoacetate (IO), tubocurarine (TC), and surgical denervation (DN) on early rigor development in broiler breast muscle. In Experiment 1, birds were either anesthetized or not with SP before receiving an injection of IO or TC or maintained as noninjected controls. Experiment 2 was identical except that a treatment of denervation of the breast muscle was added. Experiment 3 was conducted to contrast birds at 1 day (DN1) and 3 days (DN3) denervation prior to slaughter to nonoperated controls. Measurements of muscle lactate, ATP, R value (ratio of inosine to adenine nucleotides), pH, sarcomere lengths, and shear were used to evaluate treatment effects. Results for Experiment 1 showed no significant differences among treatment and control groups for ATP and lactate contents, R values, or sarcomere lengths; however, significantly lower pH and higher shear values were observed for control birds. In Experiment 2, no significant differences were observed among the treatment groups for ATP, R values, or sarcomere lengths. However, lactate and shear values were significantly lower, and pH higher, for the DN and SP treated birds. Experiment 3 resulted in lower lactate and higher pH values for the DN3 treatment in comparison with both DN1 and control groups. Results of these studies indicate that the use of SP and DN can be used to alter the early profiles of rigor development.

Research note: use of consecutive carcass rinses and a most probable number procedure to estimate salmonellae contamination of inoculated broilers.

Two similar trials were conducted to evaluate the accuracy of the whole carcass rinse technique in combination with a most probable number (MPN) procedure for estimating the number of salmonellae on postchill broilers. Birds were reared in litter-floored pens and inoculated with Salmonella typhimurium (10(8) cfu/mL) on Days 2, 7, and 14. In each of the two trials six carcasses were consecutively rinsed four times. Each carcass was rinsed with 100 mL of sterile water in sterile plastic bags using an automated shaking device. Salmonellae were enumerated using a three-tube MPN procedure in selenite cystine broth. There were no statistical differences in log10 MPN salmonellae per milliliter of recovered rinse fluid due to trial or consecutive rinse. In several cases salmonellae were not recovered in the initial rinse but were recovered from consecutive rinses of the same carcass. A large amount of variation in MPN levels of salmonellae among individual carcasses occurred within each consecutive rinse. The data suggested that only a percentage of the total salmonellae present on a postchill carcass were recovered with each consecutive rinse, and the organisms were firmly attached prior to processing.

Effects of D-mannose on incidence and levels of salmonellae in ceca and carcass samples of market age broilers.

Two similar trials were conducted to evaluate the effects of 2.5% d-mannose (DM) in the drinking water of broilers for the first 10 days on incidence and levels of salmonellae in the ceca and on the carcass at market age. Controls received drinking water with no DM. Birds were reared on used litter in floor pens and were inoculated via the drinking water with 10(8) cfu/mL Salmonella typhimurium (ATCC 14028) on Day 3. At 49 days, 60 birds per treatment were processed and the ceca contents and prechill carcass were evaluated for salmonellae incidence by the most probable number (MPN) method. Results were inconclusive: level of salmonellae in the ceca contents and carcass rinse was significantly lower in control samples than in DM samples in one of the two trials; the reverse was true in the other trial.

Mandible-like structure with teeth in an ovarian cystic teratoma.

The findings of a tooth-bearing mandible-like structure within a large ovarian dermoid cyst is reported. Although the presence of assorted teeth and bone is not uncommon in teratomatous lesions, the formation of an apparent alveolar structure possessing multiple teeth is found less often.

Multinodular versus plexiform neurilemoma of the hard palate. Report of a case.

Neurilemoma (schwannoma) is the most commonly encountered nerve sheath tumor of the oral cavity. It generally appears as a single encapsulated nodule that occasionally causes pain or discomfort. The tongue is involved most frequently, followed by the palate, floor of mouth, and buccal mucosa. Neurilemomas occur most often during the second or third decades of life. Our patient is a 21-year-old woman with a recurrence of a palatal mass that was excised 3 years earlier. Histologically the lesion appeared to be a multinodular neurilemoma, a pattern rarely reported in the oral cavity.