Abstract Serotonin (5-HT) action via the 5-HT2C receptor (5-HT2C R) provides an important modulatory influence over neurons of the prefrontal cortex (PFC), which is critically involved in disorders ...of executive function including substance use disorders. In the present study, we investigated the distribution of the 5-HT2C R in the rat prelimbic prefrontal cortex (PrL), a subregion of the medial prefrontal cortex (mPFC), using a polyclonal antibody raised against the 5-HT2C R. The expression of 5-HT2C R immunoreactivity (IR) was highest in the deep layers (layers V/VI) of the mPFC. The 5-HT2C R-IR was typically most intense at the periphery of cell bodies and the initial segment of cell processes. Approximately 50% of the 5-HT2C R-IR detected was found in glutamate decarboxylase, isoform 67 (GAD 67)-positive neurons. Of the subtypes of GABA interneurons identified by expression of several calcium-binding proteins, a significantly higher percentage of neurons expressing IR for parvalbumin also expressed 5-HT2C R-IR than did the percentage of neurons expressing calbindin-IR or calretinin-IR that also expressed 5-HT2C R-IR. Since parvalbumin is located in basket and chandelier GABA interneurons which project to cell body and initial axon segments of pyramidal cells, respectively, these results raise the possibility that the 5-HT2C R in the mPFC acts via the parvalbumin-positive GABAergic interneurons to regulate the output of pyramidal cells in the rat mPFC.
Abstract
Our understanding of the climatic teleconnections that drove ice-age cycles has been limited by a paucity of well-dated tropical records of glaciation that span several glacial–interglacial ...intervals. Glacial deposits offer discrete snapshots of glacier extent but cannot provide the continuous records required for detailed interhemispheric comparisons. By contrast, lakes located within glaciated catchments can provide continuous archives of upstream glacial activity, but few such records extend beyond the last glacial cycle. Here a piston core from Lake Junín in the uppermost Amazon basin provides the first, to our knowledge, continuous, independently dated archive of tropical glaciation spanning 700,000 years. We find that tropical glaciers tracked changes in global ice volume and followed a clear approximately 100,000-year periodicity. An enhancement in the extent of tropical Andean glaciers relative to global ice volume occurred between 200,000 and 400,000 years ago, during sustained intervals of regionally elevated hydrologic balance that modified the regular approximately 23,000-year pacing of monsoon-driven precipitation. Millennial-scale variations in the extent of tropical Andean glaciers during the last glacial cycle were driven by variations in regional monsoon strength that were linked to temperature perturbations in Greenland ice cores
1
; these interhemispheric connections may have existed during previous glacial cycles.
Elevated serum prostate specific antigen (PSA) may be the initial and only indication of disease recurrence after prostatectomy for prostate cancer. External beam radiotherapy may be given in this ...setting in an attempt to eradicate the disease but therapeutic outcomes after this approach require further description. We describe the intermediate term outcome in a large group of patients treated with radiotherapy and identify pre-therapy factors associated with disease outcome.
We retrospectively studied a cohort of 166 consecutive patients treated with radiotherapy between July 1987 and May 1996. The Kaplan-Meier method was used to describe patient outcome for the overall study group, and statistical associations of pre-therapy variables with outcome were sought to identify predictive factors.
At a median followup of 52 months 46% (95% confidence interval 38 to 55) of patients were expected to be free of biochemical relapse 5 years after radiotherapy. Multivariate analysis identified pathological classification (seminal vesicle invasion), tumor grade and pre-radiotherapy serum PSA as independent factors associated with biochemical relapse. Although in 1 of 6 patients a chronic complication was attributed to radiotherapy, it was often mild and self-limited in nature.
In our current series approximately half of the patients treated with radiotherapy for an isolated elevation of serum PSA after prostatectomy were free of biochemical relapse at 5 years of followup. Radiotherapy may be given in this setting with modest long-term morbidity.
Studies suggest that screening with spiral computed tomography can detect lung cancers at a smaller size and earlier stage than chest radiography can. To evaluate low-radiation-dose spiral computed ...tomography and sputum cytology in screening for lung cancer, we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospective cohort study. One year after baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed (22 prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum cytology alone detected 2 cases. Cell types were: squamous cell, 6; adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two patients underwent curative surgical resection. Seven benign nodules were resected. The mean size of the non-small cell cancers detected by computed tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1; IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis. Computed tomography can detect early-stage lung cancers. The rate of benign nodule detection is high.
Different source-related factors can lead to vocal fold instabilities and bifurcations referred to as voice breaks. Nonlinear coupling in phonation suggests that changes in acoustic loading can also ...be responsible for this unstable behavior. However, no in vivo visualization of tissue motion during these acoustically induced instabilities has been reported. Simultaneous recordings of laryngeal high-speed videoendoscopy, acoustics, aerodynamics, electroglottography, and neck skin acceleration are obtained from a participant consistently exhibiting voice breaks during pitch glide maneuvers. Results suggest that acoustically induced and source-induced instabilities can be distinguished at the tissue level. Differences in vibratory patterns are described through kymography and phonovibrography; measures of glottal area, open/speed quotient, and amplitude/phase asymmetry; and empirical orthogonal function decomposition. Acoustically induced tissue instabilities appear abruptly and exhibit irregular vocal fold motion after the bifurcation point, whereas source-induced ones show a smoother transition. These observations are also reflected in the acoustic and acceleration signals. Added aperiodicity is observed after the acoustically induced break, and harmonic changes appear prior to the bifurcation for the source-induced break. Both types of breaks appear to be subcritical bifurcations due to the presence of hysteresis and amplitude changes after the frequency jumps. These results are consistent with previous studies and the nonlinear source-filter coupling theory.
The electrolarynx (EL) is a common rehabilitative speech aid for individuals who have undergone total laryngectomy, but they typically lack pitch control and require the exclusive use of one hand. ...The viability of using neck and face surface electromyography (sEMG) to control the onset, offset, and pitch of an EMG-controlled EL (EMG-EL) was studied. Eight individuals who had undergone total laryngectomy produced serial and running speech using a typical handheld EL and the EMG-EL while attending to real-time visual sEMG biofeedback. Running speech tokens produced with the EMG-EL were examined for naturalness by 10 listeners relative to those produced with a typical EL using a visual analog scale. Serial speech performance was assessed as the percentage of words that were fully voiced and pauses that were successfully produced. Results of the visual analog scale assessment indicated that individuals were able to use the EMG-EL without training to produce running speech perceived as natural as that produced with a typical handheld EL. All participants were able to produce running and serial speech with the EMG-EL controlled by sEMG from multiple recording locations, with the superior ventral neck or submental surface locations providing at least one of the two best control locations.
The brain of the adult fruit fly, Drosophila melanogaster, contains tyrosine hydroxylase, the rate-limiting enzyme required for catecholamine biosynthesis, as well as dopa decarboxylase. ...Catecholamines, principally dopamine, are also present. We have previously shown that pharmacological inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine results in a dose-related inhibition of locomotor activity in adult organisms. Similar results were found with reserpine, a well-known inhibitor of catecholamine uptake into storage granules. The drug-induced inhibition could be prevented in each case by the concomitant administration of L-dopa. The single-copy gene coding for tyrosine hydroxylase in Drosophila is pale (ple). Both null and temperature-sensitive loss of function mutant alleles of ple are recessive embryonic lethals. Heterozygous null mutant flies have normal locomotor activity demonstrating that only a single dose of the wild type form of ple is required to support normal function. Both hemizygous and homozygous temperature-sensitive ple mutants (ple(ts1)) also show normal locomotor activity at the permissive temperature for this mutant allele (18 degrees C), which progressively declines as the temperature is increased to its restrictive level (29 degrees C). These abnormal locomotor effects are reversible by L-dopa. Thus the effects on locomotor activity resulting from the pharmacological inhibition of catecholamine synthesis or storage are the same as those resulting from lack of tyrosine hydroxylase expression. These findings indicate that brain catecholamine loss decreases locomotor activity in the fly, as it does in mammals, and demonstrate the ability of functional genomic studies to mimic that of pharmacological inhibition of enzyme function or other similar processes.
Magnetic resonance imaging (MRI) techniques were used to determine the effect of preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury and the level of cerebral perfusion. ...Middle cerebral artery occlusion (MCAO) was induced by a suture insertion technique. Forty one rats were divided into hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or 2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6 brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV) were estimated using gradient echo (GE) bolus tracking and steady-state spin echo (SE) imaging techniques, respectively. Brain injury correlated with the perfusion level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by 37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We conclude that preexisting hyperglycemia increases acute postischemic MRI-measurable brain cellular injury in proportion to an associated increased microvascular ischemia.
The human gene that codes for the protein alpha-synuclein has been transferred into the Drosophila melanogaster genome. The transgenic flies recapitulate some of the essential features of Parkinson's ...disease. These include the degeneration of certain dopaminergic neurons in the brain accompanied by the appearance of age-dependent abnormalities in locomotor activity. In the present study, we tested the locomotor response of these transgenic flies to prototypes of the major classes of drugs currently used to treat this disorder. A time course study was first conducted to determine when impaired locomotor activity appeared relative to normal "wild-type" flies. A climbing or negative geotaxis assay measuring the ability of the organisms to climb up the walls of a plastic vial was used. Based on the results obtained, normal and transgenic flies were treated with each of the drugs in their food for 13 days and then assayed. The activity of transgenic flies treated with L-DOPA was restored to normal. Similarly, the dopamine agonists pergolide, bromocriptine, and 2,3,4,5-tetrahydro-7,8-dihydroxy- 1-phenyl-1H-3-benzazepine (SK&F 38393) were substantially effective. Atropine, the prototypical muscarinic cholinergic receptor antagonist, was also effective but to a lesser extent than the other antiparkinson compounds. p-Chlorophenylalanine, an inhibitor of serotonin synthesis, was without beneficial effect as was alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis. This behavioral study further demonstrates the utility of this model in studying Parkinson's disease and reinforces the concept that inhibition of the action of alpha-synuclein may be useful in its treatment as may dopamine D(1) receptor agonists.
On June 8 1994, a beaver dam on Rocky Creek, a small stream in central Alberta, failed and released about 7500 m super(3) of water. The estimated peak of the resulting flood wave was 15 m super(3) s ...super(-1), which is 3.5 times the maximum discharge recorded for the creek over 23 years. The flood wave destroyed five hydrometric stations, scoured some channel reaches, and deposited sediment in others. Large trees and debris from old beaver dams were carried downstream and deposited in piles across the channel and adjacent banks. The flood wave peak was dampened to 6% of the estimated upstream flood peak as it passed through a 90-ha wetland characterized by both organic and mineral soils, sedge meadow and willow, and containing a small lake and several beaver ponds. Although the peak flow resulting from the dam outburst was extreme, the volume, most of which was probably detained in the wetland, was not. The volume amounted to only 7% of the combined basin runoff from precipitation and the beaver dam outburst. This extreme event showed that beaver activity can greatly affect the hydrology of small streams and demonstrated the importance of taking wetland storage into account when conducting hydrologic studies on watersheds that contain sizeable areas of wetlands.
PDF
