Correlates of Auditory Decision-Making in Prefrontal, Auditory, and Basal Lateral Amygdala Cortical Areas.

Spatial selective listening and auditory choice underlie important processes including attending to a speaker at a cocktail party and knowing how (or whether) to respond. To examine task encoding and the relative timing of potential neural substrates underlying these behaviors, we developed a spatial selective detection paradigm for monkeys, and recorded activity in primary auditory cortex (AC), dorsolateral prefrontal cortex (dlPFC), and the basolateral amygdala (BLA). A comparison of neural responses among these three areas showed that, as expected, AC encoded the side of the cue and target characteristics before dlPFC and BLA.

Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements.

Background The National Institute of Standards and Technology (NIST) Reference Material RM 8366 was developed to improve the quality of gene copy measurements of EGFR (epidermal growth factor receptor) and MET (proto-oncogene, receptor tyrosine kinase), important targets for cancer diagnostics and treatment. The reference material is composed of genomic DNA prepared from six human cancer cell lines with different levels of amplification of the target genes. Methods The reference values for the ratios of the EGFR and MET gene copy numbers to the copy numbers of reference genes were measured using digital PCR.

Signature Patterns for Top-Down and Bottom-Up Information Processing via Cross-Frequency Coupling in Macaque Auditory Cortex.

Predictive coding is a theoretical framework that provides a functional interpretation of top-down and bottom-up interactions in sensory processing. The theory suggests there are differences in message passing up versus down the cortical hierarchy. These differences result from the linear feedforward of prediction errors, and the nonlinear feedback of predictions.

A Comparison of Auditory Oddball Responses in Dorsolateral Prefrontal Cortex, Basolateral Amygdala, and Auditory Cortex of Macaque.

The mismatch negativity (MMN) is an ERP component seen in response to unexpected "novel" stimuli, such as in an auditory oddball task. The MMN is of wide interest and application, but the neural responses that generate it are poorly understood. This is in part due to differences in design and focus between animal and human oddball paradigms.

The Effect of Deep Brain Stimulation Therapy on Fear-Related Capture of Attention in Parkinson's Disease and Essential Tremor: A Comparison to Healthy Individuals.

In addition to motor symptoms, Parkinson's disease (PD) involves significant non-motor sequelae, including disruptions in cognitive and emotional processing. Fear recognition appears to be affected both by the course of the disease and by a common interventional therapy, deep brain stimulation of the subthalamic nucleus (STN-DBS). Here, we examined if these effects extend to other aspects of emotional processing, such as attentional capture by negative emotional stimuli.

A mutational comparison of adult and adolescent and young adult (AYA) colon cancer.

Background: It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients.

Methods: To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers.

Subthalamic nucleus deep brain stimulation affects distractor interference in auditory working memory.

Computational and theoretical accounts hypothesize the basal ganglia play a supramodal "gating" role in the maintenance of working memory representations, especially in preservation from distractor interference. There are currently two major limitations to this account. The first is that supporting experiments have focused exclusively on the visuospatial domain, leaving questions as to whether such "gating" is domain-specific.

The Effects of Dexmedetomidine on Microelectrode Recordings of the Subthalamic Nucleus during Deep Brain Stimulation Surgery: A Retrospective Analysis.

Background: The placement of subthalamic nucleus (STN) deep brain stimulation (DBS) electrodes can be facilitated by intraoperative microelectrode recording (MER) of the STN.

Objectives: Optimal anesthetic management during surgery remains unclear because of a lack of quantitative data of the effect of anesthetics on MER. Therefore, we measured the effects of dexmedetomidine (DEX) on MER measures of the STN commonly taken intraoperatively.

Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

Objectives: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task.

Certified DNA Reference Materials to Compare HER2 Gene Amplification Measurements Using Next-Generation Sequencing Methods.

The National Institute of Standards and Technology (NIST) Standard Reference Materials 2373 is a set of genomic DNA samples prepared from five breast cancer cell lines with certified values for the ratio of the HER2 gene copy number to the copy numbers of reference genes determined by real-time quantitative PCR and digital PCR. Targeted-amplicon, whole-exome, and whole-genome sequencing measurements were used with the reference material to compare the performance of both the laboratory steps and the bioinformatic approaches of the different methods using a range of amplification ratios. Although good reproducibility was observed in each next-generation sequencing method, slightly different HER2 copy numbers associated with platform-specific biases were obtained.

RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing.

With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon.

Plasmid-Based Materials as Multiplex Quality Controls and Calibrators for Clinical Next-Generation Sequencing Assays.

Although next-generation sequencing technologies have been widely adapted for clinical diagnostic applications, an urgent need exists for multianalyte calibrator materials and controls to evaluate the performance of these assays. Control materials will also play a major role in the assessment, development, and selection of appropriate alignment and variant calling pipelines. We report an approach to provide effective multianalyte controls for next-generation sequencing assays, referred to as the control plasmid spiked-in genome (CPSG).

Robustness of Next Generation Sequencing on Older Formalin-Fixed Paraffin-Embedded Tissue.

Next Generation Sequencing (NGS) technologies are used to detect somatic mutations in tumors and study germ line variation. Most NGS studies use DNA isolated from whole blood or fresh frozen tissue. However, formalin-fixed paraffin-embedded (FFPE) tissues are one of the most widely available clinical specimens.

Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants.

Parkinson's disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits.

Binaural interference: effects of temporal interferer fringe and interstimulus interval.

Binaural interference refers to the phenomenon in which the potency of binaural cues conveyed by a "target" stimulus occupying one spectral region is degraded by the presence of an "interferer" stimulus occupying a spectral region remote from the target. It is typified by conditions in which thresholds for detection of interaural temporal difference conveyed by a high-frequency target are elevated when the target is accompanied by a spectrally remote low-frequency interferer. This study explored effects of temporal relations between targets and interferers on binaural interference.

Feedforward and feedback projections of caudal belt and parabelt areas of auditory cortex: refining the hierarchical model.

Our working model of the primate auditory cortex recognizes three major regions (core, belt, parabelt), subdivided into thirteen areas. The connections between areas are topographically ordered in a manner consistent with information flow along two major anatomical axes: core-belt-parabelt and caudal-rostral. Remarkably, most of the connections supporting this model were revealed using retrograde tracing techniques.

Methods for Surgical Targeting of the STN in Early-Stage Parkinson's Disease.

Patients with Parkinson's disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn-Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort.

LONG-TERM MONITORING OF THE PHYSICOCHEMICAL PROPERTIES OF SILICA-BASED NANOPARTICLES ON THE RATE OF ENDOCYTOSIS AND EXOCYTOSIS AND CONSEQUENCES OF CELL DIVISION.

Nanomaterials are diverse in size, shape and charge and these differences likely alter their physicochemical properties in biological systems. We have investigated how these properties alter the initial and long-term dynamics of endocytosis, cell viability, cell division, exocytosis, and interaction with a collagen extracellular matrix using silica-based fluorescent nanoparticles and the murine pre-osteoblast cell line, MC3T3-E1. Three surface modified nanoparticles were analyzed: positively charged (PTMA), negatively charged (OH), and neutrally charged polyethylene glycol (PEG).

An integrated understanding of the physiological response to elevated extracellular phosphate.

Recent studies have suggested that changes in serum phosphate levels influence pathological states associated with aging such as cancer, bone metabolism, and cardiovascular function, even in individuals with normal renal function. The causes are only beginning to be elucidated but are likely a combination of endocrine, paracrine, autocrine, and cell autonomous effects. We have used an integrated quantitative biology approach, combining transcriptomics and proteomics to define a multi-phase, extracellular phosphate-induced, signaling network in pre-osteoblasts as well as primary human and mouse mesenchymal stromal cells.

Neural latencies across auditory cortex of macaque support a dorsal stream supramodal timing advantage in primates.

Sensory systems across the brain are specialized for their input, yet some principles of neural organization are conserved across modalities. The pattern of anatomical connections from the primate auditory cortex to the temporal, parietal, and prefrontal lobes suggests a possible division into dorsal and ventral auditory processing streams, with the dorsal stream originating from more caudal areas of the auditory cortex, and the ventral stream originating from more rostral areas. These streams are hypothesized to be analogous to the well-established dorsal and ventral streams of visual processing.

The effects of thiazolidinediones on human bone marrow stromal cell differentiation in vitro and in thiazolidinedione-treated patients with type 2 diabetes.

Thiazolidinedione (TZD) therapy has been associated with an increased risk of bone fractures. Studies in rodents have led to a model in which decreased bone quality in response to TZDs is due to a competition of lineage commitment between osteoblasts (OBs) and adipocytes (ADs) for a common precursor cell, resulting in decreased OB numbers. Our goal was to investigate the effects of TZD exposure on OB-AD lineage determination from primary human bone marrow stromal cells (hBMSCs) both in vitro and in vivo from nondiabetic subjects and patients with type 2 diabetics.

Bioactive silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and enhance bone mineral density in vivo.

Bone is a dynamic tissue that undergoes renewal throughout life in a process whereby osteoclasts resorb worn bone and osteoblasts synthesize new bone. Imbalances in bone turnover lead to bone loss and development of osteoporosis and ultimately fracture, a debilitating condition with high morbidity and mortality. Silica is a ubiquitous biocontaminant that is considered to have high biocompatibility.

Auditory cortical tuning to band-pass noise in primate A1 and CM: a comparison to pure tones.

We examined multiunit responses to tones and to 1/3 and 2/3 octave band-pass noise (BPN) in the marmoset primary auditory cortex (A1) and the caudomedial belt (CM). In both areas, BPN was more effective than tones, evoking multiunit responses at lower intensity and across a wider frequency range. Typically, the best responses to BPN remained at the characteristic frequency.

Identification of the homeobox protein Prx1 (MHox, Prrx-1) as a regulator of osterix expression and mediator of tumor necrosis factor α action in osteoblast differentiation.

Tumor necrosis factor α (TNF-α) promotes bone loss and inhibits bone formation. Osterix (Osx, SP7) is a transcription factor required for osteoblast (OB) differentiation because deletion results in a cartilaginous skeleton. We previously described a TNF suppressor element in the Osx promoter that was used to isolate nuclear proteins mediating TNF inhibition of OB differentiation.