Early Evidence of Maya Hieroglyphic Writing at Kichpanha, Belize

Archaeological research, conducted intermittently at Kichpanha, Belize, from 1973 to 1983 was primarily limited to surveying and mapping. During the 1985 season, test excavations initiated in the 1983 season were continued (Gibson 1985a). House mounds and plazuela groups yielded further evidence of extensive use of the site from the Xe and early facet Mamom phases (relatively dated to approximately 900-700 B.C.), until its near total abandonment in the Early Postclassic (ca. A.D. 900-1000). In this paper we present some preliminary results of the 1985 season at Kichpanha in the context of our research foci which included economic relationships with the lithic industrial site of Colha to the south and identifying the subsistence base of Kichpanha

Effect of Aspartame-Derived Phenylalanine on Neutral Amino Acid Uptake in Human Brain: A Positron Emission Tomography Study

The possible effects of elevation of the plasma phe-nylalanine level secondary to the ingestion of aspartame on brain amino acid uptake in human subjects have been investigated by means of positron emission tomography (PET). 1-[ 11 C]Aminocyclohexanecarboxylate ([ 11 C]ACHC) is a poorly metabolized synthetic amino acid that crosses the blood-brain barrier by the same carrier that transports naturally occurring large neutral amino acids. Quantitative test-retest PET studies were performed on 15 individuals. Seven received two identical baseline scans, whereas eight received a baseline scan followed by a scan performed ∼40–45 min following ingestion of an orange-flavored beverage containing 34 mg/kg of body weight of the low-calorie sweetener aspartame, a dose equivalent to the amount in 5 L of diet soft drink consumed all at once by the study subjects, weighing an average of 76 kg. The 40–45-min interval was selected to maximize the detection of possible decreases in ACHC uptake resulting from increased competition for the carrier, because the plasma phenylalanine level is known to peak at this time. We observed an 11.5% decrease in the amino acid transport rate constant Kt and a smaller decrease in the tissue distribution volume of ACHC (6%). Under conditions of normal dietary use, aspartame is thus unlikely to cause changes in brain amino acid uptake that are measurable by PET.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65668/1/j.1471-4159.1991.tb02047.x.pd

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts

Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability

Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer's disease (AD) by validating biomarkers for AD clinical trials. METHODS: We searched for ADNI publications using established methods. RESULTS: ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson's disease and multiple sclerosis. DISCUSSION: ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

INTRODUCTION: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. METHODS: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. RESULTS: Multimodal analyses will provide insight into AD pathophysiology and disease progression. DISCUSSION: ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments

The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)

Objective: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. Methods: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. Results: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. Conclusions: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Influences of Biological and Adoptive Mothers’ Depression and Antisocial Behavior on Adoptees' Early Behavior Trajectories

Research clearly demonstrates that parents pass risk for depression and antisocial behavior on to their children. However, most research confounds genetic and environmental mechanisms by studying genetically related individuals. Furthermore, most studies focus on either depression or antisocial behavior in parents or children, despite evidence of co-occurrence and shared etiology, and few consider the early origins of these problems in childhood. We estimated the influence of biological and adoptive mothers’ depression and antisocial behavior on growth in child externalizing and internalizing behaviors across early childhood using data from a prospective adoption study. Participants were 346 matched triads of physically healthy children (196 boys; 150 girls), biological mothers (BM), and adoptive mothers (AM). Latent growth curve models were estimated using AM reports of child internalizing and externalizing behaviors at ages 18, 27, and 54 months. Predictors of intercept (18 months) but not slope were identified. BM lifetime histories of major depressive disorder predicted child externalizing behaviors and BM antisocial behavior predicted child internalizing behavior. AM depressive symptoms and antisocial behavior were associated with both child outcomes. AM paths, but not BM paths were partially replicated using adopted fathers’ reports of child outcomes. BM obstetric complications, prenatal depressive symptoms, and postnatal adoptive family contact with BM did not account for BM paths. This adoption study distinguished risks conferred by biological mothers’ depression and antisocial behavior to children’s behaviors from those associated with adoptive mothers’ related symptoms. Future studies should examine gene-environment interplay to explain the emergence of serious problem trajectories in later childhood.Keywords: depression, externalizing, adoption, genetic risk, early childhood, internalizin

"They go for gender first"

There have been many recent media reports about the online harassment of women journalists working in technology, particularly the video gaming industry. However, little research has focused on this aspect, by looking at specific occupations, or analysing the implications for women and society. This paper is a feminist study of the experiences of sexist abuse of a sample of women journalists writing about technology. It is a commentary on the results of a questionnaire-based study of 102 women (and their approximately 300 comments) that work in what has emerged as one of the frontlines of the struggle for gender equality. The research looks at the extent of the abuse, the harm it causes and how women are reacting to it. Most of the participants have experienced abuse, many have changed their working practices and some have disguised their identity to avoid it. An examination of their comments suggests that sexist abuse is now often normalised, alongside a new kind of "invisible" feminism. It also reveals a mood of defiance and an appetite for radical change to address the problems of exclusion and loss of identity. Overall, results indicate that the abuse is damaging women’s lives and impacting journalism and society in a negative way