Regulation of glutamate release by heteromeric nicotinic receptors in layer V of the secondary motor region (Fr2) in the dorsomedial shoulder of prefrontal cortex in mouse

We studied how nicotinic acetylcholine receptors (nAChRs) regulate glutamate release in the secondary motor area (Fr2) of the dorsomedial murine prefrontal cortex, in the presence of steady agonist levels. Fr2 mediates response to behavioral situations that require immediate attention and is a candidate for generating seizures in the frontal epilepsies caused by mutant nAChRs. Morphological analysis showed a peculiar chemoarchitecture and laminar distribution of pyramidal cells and interneurons. Tonic application of 5 µM nicotine on Layer V pyramidal neurons strongly increased the frequency of spontaneous glutamatergic excitatory postsynaptic currents. The effect was inhibited by 1 µM dihydro‐β‐erythroidine (which blocks α4‐containing nAChRs) but not by 10 nM methyllicaconitine (which blocks α7‐containing receptors). Excitatory postsynaptic currents s were also stimulated by 5‐iodo‐3‐[2(S)‐azetidinylmethoxy]pyridine, selective for β2‐containing receptors, in a dihydro‐β‐erythroidine ‐sensitive way. We next studied the association of α4 with different populations of glutamatergic terminals, by using as markers the vesicular glutamate transporter type (VGLUT) 1 for corticocortical synapses and VGLUT2 for thalamocortical projecting fibers. Immunoblots showed higher expression of α4 in Fr2, as compared with the somatosensory cortex. Immunofluorescence showed intense VGLUT1 staining throughout the cortical layers, whereas VGLUT2 immunoreactivity displayed a more distinct laminar distribution. In Layer V, colocalization of α4 nAChR subunit with both VGLUT1 and VGLUT2 was considerably stronger in Fr2 than in somatosensory cortex. Thus, in Fr2, α4β2 nAChRs are expressed in both intrinsic and extrinsic glutamatergic terminals and give a major contribution to control glutamate release in Layer V, in the presence of tonic agonist levels. Synapse 00:000–000, 2013 . © 2013 Wiley Periodicals, Inc.     

Multiple independent origins of mitochondrial gene order in birds

Mitochondrial genomes of all vertebrate animals analyzed to date have the same 37 genes, whose arrangement in the circular DNA molecule varies only in the relative position of a few genes. This relative conservation suggests that mitochondrial gene order characters have potential utility as phylogenetic markers for higher-level vertebrate taxa. We report discovery of a mitochondrial gene order that has had multiple independent originations within birds, based on sampling of 137 species representing 13 traditionally recognized orders. This provides evidence of parallel evolution in mitochondrial gene order for animals. Our results indicate operation of physical constraints on mitochondrial gene order changes and support models for gene order change based on replication error. Bird mitochondria have a displaced O_L (origin of light-strand replication site) as do various other Reptilia taxa prone to gene order changes. Our findings point to the need for broad taxonomic sampling in using mitochondrial gene order for phylogenetic analyses. We found, however, that the alternative mitochondrial gene orders distinguish the two primary groups of songbirds (order Passeriformes), oscines and suboscines, in agreement with other molecular as well as morphological data sets. Thus, although mitochondrial gene order characters appear susceptible to some parallel evolution because of mechanistic constraints, they do hold promise for phylogenetic studies.     

Severe α-Thalassemia Intermedia Due to a Compound Heterozygosity for the Highly Unstable Hb Adana (HBA2: c.179G>A) and a Novel Codon 24 (HBA2: c.75T>A) Mutation

We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T?>?A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G?>?A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.     

Low prevalence of patellar tendon abnormality and low incidence of patellar tendinopathy in female collegiate volleyball players

ABSTRACT

The prevalence of patellar tendinopathy has been reported to be as high as 50% in elite male volleyball (VB) players; however, the rate of injury in female collegiate VB athletes is unknown. The purpose of this study was to 1) identify the prevalence of ultrasonographic evidence of patellar tendon abnormality at the start of the preseason in female collegiate VB players; 2) report the incidence of tendinopathy during the season; and 3) determine if the preseason presence of tendon abnormality is associated with onset of disease. One hundred and six female collegiate VB players had both patellar tendons imaged. Incidence of patellar tendinopathy was tracked during the course of the 4-month season. Twenty-two athletes presented with ultrasonographic evidence of patellar tendon abnormality in at least one knee at the start of the preseason. The incidence of time-loss patellar tendinopathy was 0.26 (95% CI: 0.04, 0.85) per 1000 athletic exposures. This study was unable to determine if preseason presence of tendon abnormality was associated with a greater risk of tendinopathy due to power. The prevalence of tendon abnormality in the preseason and the incidence of patellar tendinopathy in female collegiate VB players are lower than that observed in other populations.     

Generalizability of machine learning for classification of schizophrenia based on resting‐state functional MRI data

Machine learning has increasingly been applied to classification of schizophrenia in neuroimaging research. However, direct replication studies and studies seeking to investigate generalizability are scarce. To address these issues, we assessed within‐site and between‐site generalizability of a machine learning classification framework which achieved excellent performance in a previous study using two independent resting‐state functional magnetic resonance imaging data sets collected from different sites and scanners. We established within‐site generalizability of the classification framework in the main data set using cross‐validation. Then, we trained a model in the main data set and investigated between‐site generalization in the validated data set using external validation. Finally, recognizing the poor between‐site generalization performance, we updated the unsupervised algorithm to investigate if transfer learning using additional unlabeled data were able to improve between‐site classification performance. Cross‐validation showed that the published classification procedure achieved an accuracy of 0.73 using majority voting across all selected components. External validation found a classification accuracy of 0.55 (not significant) and 0.70 (significant) using the direct and transfer learning procedures, respectively. The failure of direct generalization from one site to another demonstrates the limitation of within‐site cross‐validation and points toward the need to incorporate efforts to facilitate application of machine learning across multiple data sets. The improvement in performance with transfer learning highlights the importance of taking into account the properties of data when constructing predictive models across samples and sites. Our findings suggest that machine learning classification result based on a single study should be interpreted cautiously.     

Virtual Resection: A New Tool for Preparing for Nephron-Sparing Surgery in Wilms Tumor Patients

Nephron-sparing surgery (NSS) in Wilms tumor (WT) patients is a surgically challenging procedure used in highly selective cases only. Virtual resections can be used for preoperative planning of NSS to estimate the remnant renal volume (RRV) and to virtually mimic radical tumor resection. In this single-center evaluation study, virtual resection for NSS planning and the user experience were evaluated. Virtual resection was performed in nine WT patient cases by two pediatric surgeons and one pediatric urologist. Pre- and postoperative MRI scans were used for 3D visualization. The virtual RRV was acquired after performing virtual resection and a questionnaire was used to assess the ease of use. The actual RRV was derived from the postoperative 3D visualization and compared with the derived virtual RRV. Virtual resection resulted in virtual RRVs that matched nearly perfectly with the actual RRVs. According to the questionnaire, virtual resection appeared to be straightforward and was not considered to be difficult. This study demonstrated the potential of virtual resection as a new planning tool to estimate the RRV after NSS in WT patients. Future research should further evaluate the clinical relevance of virtual resection by relating it to surgical outcome.     

Assignment test method using hypervariable markers for blue marlin (Makaira nigricans) stock identification

Blue marlin (Makaira nigricans) stock status varies among ocean basins, and the Atlantic-wide stock is overfished. United States regulations prohibit commercial landing, importation and sale of Atlantic blue marlin, but not of Pacific or Indian Ocean conspecifics. We genotyped 344 blue marlin of known origin and 16 samples used as unknowns at 13 microsatellite loci and the mitochondrial control region. Assignment tests were conducted using GENECLASS2 to investigate the efficacy of available genotypic data to identify individual origin. We successfully discriminated Atlantic and Pacific blue marlin using genetic characters, providing more power to assign marketed blue marlin products to ocean of origin.