Acoustic Enhancement of Sleep Slow Oscillations and Concomitant Memory Improvement in Older Adults.

Acoustic stimulation methods applied during sleep in young adults can increase slow wave activity (SWA) and improve sleep-dependent memory retention. It is unknown whether this approach enhances SWA and memory in older adults, who generally have reduced SWA compared to younger adults. Additionally, older adults are at risk for age-related cognitive impairment and therefore may benefit from non-invasive interventions.

A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction.

Mutations in the gene encoding tau (MAPT) cause frontotemporal dementia spectrum disorders. A rare tau variant p.A152T was reported as a risk factor for frontotemporal dementia spectrum and Alzheimer's disease in an initial case-control study.

Variations in Acetylcholinesterase Activity within Human Cortical Pyramidal Neurons Across Age and Cognitive Trajectories.

We described an extensive network of cortical pyramidal neurons in the human brain with abundant acetylcholinesterase (AChE) activity. Emergence of these neurons during childhood/adolescence, attainment of highest density in early adulthood, and virtual absence in other species led us to hypothesize involvement of AChE within these neurons in higher cortical functions. The current study quantified the density and staining intensity of these neurons using histochemical procedures.

Knee morphometric and alignment measurements with MR imaging in young adults with central cartilage lesions of the patella and trochlea.

Purpose: The goal of this study was to assess whether common measurements of patellar and trochlear morphology and patellar alignment are associated with central cartilage lesions of the patella and trochlea using magnetic resonance imaging (MRI).

Methods: The MRI examinations of 58 patients (38 women, 20 men; mean age, 28.59 years [range: 19-35 years]) with central cartilage lesions of the patella and trochlea were retrospectively compared to those obtained in 102 control subjects (57 women, 45 men; mean age, 27.

Reactive sites and course of reduction in the Rieske protein.

Rieske proteins play an essential role in electron transfer in the bc complex. Rieske proteins contain a [2Fe-2S] cluster with one iron ligated by two histidines and the other iron ligated by two cysteines. All Rieske proteins have pH-dependent reduction potentials with the histidines ligating the cluster deprotonating in response to increases in pH.

Cerebrospinal fluid markers detect Alzheimer's disease in nonamnestic dementia.

Introduction: The accuracy of cerebrospinal fluid (CSF) biomarkers for detecting Alzheimer's disease (AD) pathology has not been fully validated in autopsied nonamnestic dementias.

Methods: We retrospectively evaluated CSF amyloid β 1-42, phosphorylated-tau, and amyloid-tau index as predictors of Alzheimer pathology in patients with primary progressive aphasia, frontotemporal dementia, and progressive supranuclear palsy.

Results: Nineteen nonamnestic autopsied cases with relevant CSF values were included.

Diazepam in the Treatment of Moderate to Severe Alcohol Withdrawal.

Benzodiazepines ameliorate or prevent the symptoms and complications of moderate to severe alcohol withdrawal, which can include autonomic hyperactivity, agitation, combativeness, hallucinations, seizures, delirium, and death. The benzodiazepines most commonly used for this purpose are lorazepam, chlordiazepoxide, oxazepam, and diazepam. It is widely asserted that no member of this group is superior to the others for treatment of alcohol withdrawal.

ABRF Proteome Informatics Research Group (iPRG) 2015 Study: Detection of Differentially Abundant Proteins in Label-Free Quantitative LC-MS/MS Experiments.

Detection of differentially abundant proteins in label-free quantitative shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments requires a series of computational steps that identify and quantify LC-MS features. It also requires statistical analyses that distinguish systematic changes in abundance between conditions from artifacts of biological and technical variation. The 2015 study of the Proteome Informatics Research Group (iPRG) of the Association of Biomolecular Resource Facilities (ABRF) aimed to evaluate the effects of the statistical analysis on the accuracy of the results.

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons.

Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR.

Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1.

Every data-rich community research effort requires a clear plan for ensuring the quality of the data interpretation and comparability of analyses. To address this need within the Human Proteome Project (HPP) of the Human Proteome Organization (HUPO), we have developed through broad consultation a set of mass spectrometry data interpretation guidelines that should be applied to all HPP data contributions. For submission of manuscripts reporting HPP protein identification results, the guidelines are presented as a one-page checklist containing 15 essential points followed by two pages of expanded description of each.

Identification of Essential Genes in the Salmonella Phage SPN3US Reveals Novel Insights into Giant Phage Head Structure and Assembly.

Unlabelled: Giant tailed bacterial viruses, or phages, such as Pseudomonas aeruginosa phage ϕKZ, have long genomes packaged into large, atypical virions. Many aspects of ϕKZ and related phage biology are poorly understood, mostly due to the fact that the functions of the majority of their proteins are unknown. We hypothesized that the Salmonella enterica phage SPN3US could be a useful model phage to address this gap in knowledge.

Retinal nerve fiber layer thickness in amnestic mild cognitive impairment: Case-control study and meta-analysis.

Introduction: Retinal structural changes in subjects with mild cognitive impairment (MCI) remain a subject of controversy.

Methods: We investigated the correlation between optical coherence tomography (OCT) of the retinal sublayers, including the retinal nerve fiber layer (RNFL), and cognitive function in subjects with amnestic MCI and compared the OCT findings with matched controls. We also performed a meta-analysis of the world literature using a random-effects model.

Aphasic variant of Alzheimer disease: Clinical, anatomic, and genetic features.

Objective: To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD.

Methods: A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set.

Design and synthesis of novel protein kinase R (PKR) inhibitors.

Protein kinase RNA-activated (PKR) plays an important role in a broad range of intracellular regulatory mechanisms and in the pathophysiology of many human diseases, including microbial and viral infections, cancer, diabetes and neurodegenerative disorders. Recently, several potent PKR inhibitors have been synthesized. However, the enzyme's multifunctional character and a multitude of PKR downstream targets have prevented the successful transformation of such inhibitors into effective drugs.

FGF19 functions as autocrine growth factor for hepatoblastoma.

Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis.

Response to Bodin and Grote regarding postdoctoral recruitment in clinical neuropsychology.

Bodin and Grote convey their opinion that the field of clinical neuropsychology would be best served by a match system for recruitment into postdoctoral training. We critically review their arguments and offer an alternative point of view. Our view considers the current state of the match system in neuropsychology, incorporates comparisons with other disciplines that rely on a match system, and addresses the role of postdoctoral training and the specialization that takes shape at this level.

Using quantile regression to create baseline norms for neuropsychological tests.

Introduction: The Uniform Data Set (UDS) contains neuropsychological test scores and demographic information for participants at Alzheimer's disease centers across the United States funded by the National Institute on Aging. Mean regression analysis of neuropsychological tests has been proposed to detect cognitive decline, but the approach requires stringent assumptions.

Methods: We propose using quantile regression to directly model conditional percentiles of neuropsychological test scores.

Greazy: Open-Source Software for Automated Phospholipid Tandem Mass Spectrometry Identification.

Lipid identification from data produced with high-throughput technologies is essential to the elucidation of the roles played by lipids in cellular function and disease. Software tools for identifying lipids from tandem mass (MS/MS) spectra have been developed, but they are often costly or lack the sophistication of their proteomics counterparts. We have developed Greazy, an open source tool for the automated identification of phospholipids from MS/MS spectra, that utilizes methods similar to those developed for proteomics.

Neuropathologic Associations of Learning and Memory in Primary Progressive Aphasia.

Importance: The dementia syndrome of primary progressive aphasia (PPA) can be caused by 1 of several neuropathologic entities, including forms of frontotemporal lobar degeneration (FTLD) or Alzheimer disease (AD). Although episodic memory is initially spared in this syndrome, the subtle learning and memory features of PPA and their neuropathologic associations have not been characterized.

Objective: To detect subtle memory differences on the basis of autopsy-confirmed neuropathologic diagnoses in PPA.

Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.

Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors.

Scale-dependent linkages between nitrate isotopes and denitrification in surface soils: implications for isotope measurements and models.

Natural abundance nitrate (NO3 (-)) isotopes represent a powerful tool for assessing denitrification, yet the scale and context dependence of relationships between isotopes and denitrification have received little attention, especially in surface soils. We measured the NO3 (-) isotope compositions in soil extractions and lysimeter water from a semi-arid meadow and lawn during snowmelt, along with the denitrification potential, bulk O2, and a proxy for anaerobic microsites. Denitrification potential varied by three orders of magnitude and the slope of δ(18)O/δ(15)N in soil-extracted NO3 (-) from all samples measured 1.

Mild cognitive impairment in Parkinson's disease versus Alzheimer's disease.

Introduction: No known studies have compared longitudinal characteristics between individuals with incident mild cognitive impairment due to Parkinson's disease (PD-MCI) versus Alzheimer's Disease (AD-MCI).

Methods: We used longitudinal data from the National Alzheimer's Coordinating Center's Uniform Data Set to compare 41 PD-MCI and 191 AD-MCI participants according to their demographics, presence of ≥1 APOE e4 allele, and baseline and change over time in clinical characteristics, neuropsychological test scores, and Clinical Dementia Rating sum of boxes (CDR-SB). Multivariable linear regression models with generalized estimating equations were used to account for clustered data and to test for baseline and longitudinal differences in neuropsychological test scores.

Sexual dimorphism in activation of placental autophagy in obese women with evidence for fetal programming from a placenta-specific mouse model.

The incidence of maternal obesity and its co-morbidities (diabetes, cardiovascular disease) continues to increase at an alarming rate, with major public health implications. In utero exposure to maternal obesity has been associated with development of cardiovascular and metabolic diseases in the offspring as a result of developmental programming. The placenta regulates maternal-fetal metabolism and shows significant changes in its function with maternal obesity.

Protein S-Glutathionylation Mediates Macrophage Responses to Metabolic Cues from the Extracellular Environment.

Aims: Protein S-glutathionylation, the formation of a mixed disulfide between glutathione and protein thiols, is an oxidative modification that has emerged as a new signaling paradigm, potentially linking oxidative stress to chronic inflammation associated with heart disease, diabetes, cancer, lung disease, and aging. Using a novel, highly sensitive, and selective proteomic approach to identify S-glutathionylated proteins, we tested the hypothesis that monocytes and macrophages sense changes in their microenvironment and respond to metabolic stress by altering their protein thiol S-glutathionylation status.

Results: We identified over 130 S-glutathionylated proteins, which were associated with a variety of cellular functions, including metabolism, transcription and translation, protein folding, free radical scavenging, cell motility, and cell death.