bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Abdominal Adiposity and Exercise Tolerance in Children With Obesity
Authors: Druce Axley Jennifer , Werk Lloyd N.
Published: July 2016

Purpose:

To determine whether abdominal obesity is associated with lower exercise tolerance in children.

Methods:

Waist-to-height ratios (WHtRs) were determined for 50 children aged 8 to 12 years with body mass index greater than the 95th percentile and 6-minute walk distance (6MWD) conducted.

Results:

Mean 6MWD was found to be 510 (standard deviation = 60) m. Univariate analysis revealed that WHtR was the only significant predictor of 6MWD (P = .01). In modeling using multiple regression analysis, 26% of the variance in 6MWD could be attributed to the participant's age, WHtR, and sex; WHtR was the only significant contributor to 6MWD (P = .001).

Conclusion:

WHtR was the most strongly correlated factor with distance achieved on the 6-minute walk test, a measure of exercise tolerance, and is an important measure to screen for cardiovascular disease risk and to prompt further evaluation of functional exercise capacity.
Psychotherapy and Its Role in Psychiatric Practice: A Position Paper. II. Objective, Subjective, and Intersubjective Science
Authors: SHAPIRO YAKOV , JOHN NICHOLAS , SCOTT ROWAN , TOMY NADIA
Published: July 2016

In the first article in this 2-part series, we outlined a psychobiological model of psychiatric treatment and reviewed the evidence showing psychotherapy to be a form of biological intervention that induces lasting alterations in brain structure and function. In this second article, we focus on the adaptive model of psychopathology, the effectiveness of psychotherapeutic interventions, the synergistic effects of combined psychotherapy and psychopharmacology treatments, and attention to the patient’s subjective experience and the doctor-patient alliance to complement an “objective” case formulation. The evidence strongly suggests the need for an integrated treatment approach based on the objective, subjective, and intersubjective science that forms the foundation of psychiatry as a clinical discipline, in which psychotherapy and psychopharmacology are seen as complementary treatments within a systemic approach to psychiatric care and training. What emerges is the integrated psychobiological model of care with a complex treatment matrix unique to each patient-provider pair and comprised of biological, experiential, and relational domains of treatment which form the foundation of psychiatry as a science of attachment and meaning.
Pseudocide: A Case Report
Authors: COFFEY M. JUSTIN , AHMEDANI BRIAN K.
Published: July 2016

The authors describe a case of “pseudocide” in which the patient appears to have feigned his own suicide. This case was identified as a result of a routine reconciliation of internally collected suicide data with government-collected mortality data. The authors discuss the evolution of the concept of pseudocide in the clinical literature and consider issues related to deceitful and factitious behaviors and suicide surveillance and measurement.
All Alone Together: Case Report of Folie à Trois With Schizoaffective and Negative Symptoms in Monozygotic Triplets
Authors: PAPANASTASIOU ARTEMIS , KONSTANTINOU GERASIMOS , VLACHOS THEMISTOCLES
Published: July 2016

We present a case of folie à trois with schizoaffective and negative symptoms in monozygotic triplets, which to our knowledge is unique. For 4 years starting in their late teens, the 3 male siblings withdrew socially, adopted a primitive lifestyle, and exhibited poor self-care with increasing aggression, which led to their admission to the hospital at the age of 22 years. Over the subsequent 8 years, 1 brother recovered fully with treatment, resumed academic and social functioning, and does not need medication therapy currently. The other 2 brothers have disengaged from clinical care and moved back in together, following a socially isolated, disengaged way of life. They have relapsed gradually, displaying their previous symptomatology of suspiciousness, grandiosity, irritability, and affective flattening. This case demonstrates that shared psychosis can merge with endogenous psychopathology, including negative symptoms, in the context of genetic susceptibility. In closely associated individuals, such phenomena may go unnoticed or be misinterpreted, and therefore not receive appropriate management. In such a situation, separation as a part of the treatment plan should be approached gradually in combination with a therapy that emphasizes each patient as a separate individual.
Commentary on 2 Unusual Cases
Authors: KAHN DAVID A.
Published: July 2016

Two cases of unusual situations are discussed: one involving feigned suicide detected as false only after a comparison of surveillance systems, and one involving monozygotic triplets who all developed psychosis with shared delusions. Although these 2 cases involve presentations most of us will never encounter as clinicians, they nevertheless serve to highlight fundamental questions about the nature of psychopathology. Both cases also have compelling parallels in literature and film.
Therapeutic Alliance in Patients With Schizophrenia: Introduction of a New Rating Instrument
Authors: WIDSCHWENDTER CHRISTIAN G. , HOFER ALEX , BAUMGARTNER SUSANNE , EDLINGER MONIKA , KEMMLER GEORG , RETTENBACHER MARIA A.
Published: July 2016

Objective:

The quality of the patient-psychiatrist relationship can be seen as a cornerstone of adherence to medications in patients with chronic psychiatric disorders. Although therapeutic alliance in psychotherapy has been investigated broadly, it has received little attention in the context of medication adherence. The goal of this study was to develop and validate a user-friendly questionnaire for the assessment of therapeutic alliance in clinically stable outpatients with schizophrenia.

Methods:

The “Brief Questionnaire on Therapeutic Alliance” (BQTA) addresses both the physician and the patient, each of whom responds to 5 items that focus on important domains of the therapeutic alliance. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and patients’ attitudes toward the illness and medication were assessed using the Drug Attitude Inventory (DAI).

Results:

A total of 61 patients who met ICD-10 criteria for schizophrenia spectrum disorders and their treating psychiatrists were included in the study. Overall, patients and psychiatrists gave high (ie, favorable) ratings on all BQTA items. The 5 patient-related items showed high internal consistency (Cronbach α=0.77), whereas physician-related items showed slightly less internal consistency (Cronbach α=0.68). The concordance between patient and physician ratings was fair, although statistically significant (κ=0.33, P=0.007). Physicians’ total score on the BQTA was moderately correlated with patients’ PANSS total score and with the DAI total score and its compliance subscale, whereas patients’ total score on the BQTA did not correlate with DAI or PANSS scores.

Conclusion:

The BQTA was found to cover crucial aspects of the doctor-patient relationship in chronically ill individuals with schizophrenia. Further validation will shed more light on the usefulness of this questionnaire.
Reciprocal Relationship Between Sleep Macrostructure and Evening and Morning Cellular Inflammation in Rheumatoid Arthritis
Authors: Bjurström Martin F. , Olmstead Richard , Irwin Michael R.
Published: July 2016

Objective

This study examined the reciprocal associations between sleep macrostructure and levels of cellular inflammation in rheumatoid arthritis (RA) patients and controls.

Methods

RA patients (n = 24) and matched controls (n = 48) underwent all-night polysomnography, along with assessment of spontaneous- and Toll-like receptor-4–stimulated monocytic production of tumor necrosis factor α (TNF) and interleukin (IL)-6 at 11:00 pm and 8:00 am.

Results

As compared with controls, RA patients showed lower levels of sleep efficiency (mean [standard deviation], 88.1 [6.1] versus 83.8 [7.0]), a higher percentage stage 3 sleep (9.3 [6.4] versus 13.1 [6.9]), and higher levels of percentage of monocytes either spontaneously expressing TNF at 11:00 pm (log transformed, 1.07 [0.28] versus 1.22 [0.17]), and higher Toll-like receptor-4–stimulated production of IL6 at 8:00 am (log transformed, 3.45 [0.80] versus 3.83 [0.39]). Higher levels of stimulated production of TNF at 11:00 pm were associated with higher sleep efficiency (0.74). In turn, sleep efficiency had a countervailing relationship on TNF production at 8:00 am (−0.64). Higher levels of spontaneous and stimulated production of IL6 at 11:00 pm were associated with more stage 3 (0.39), stage 4 (0.43), and slow-wave sleep (0.49), with evidence that stage 4 had a countervailing relationship on IL6 production at 8:00 am (−0.60).

Conclusions

RA patients show evidence of sleep fragmentation, greater sleep depth, and higher levels of cellular inflammation. Sleep maintenance and sleep depth show countervailing relationships with evening and morning levels of monocytic production of TNF and IL-6, respectively, which support the hypothesis of a feedback loop between sleep maintenance, slow-wave sleep, and cellular inflammation that is cytokine specific.
Life-Course Socioeconomic Position and Hippocampal Atrophy in a Prospective Cohort of Older Adults
Authors: Elbejjani Martine , Fuhrer Rebecca , Abrahamowicz Michal , Mazoyer Bernard , Crivello Fabrice , Tzourio Christophe , Dufouil Carole
Published: July 2016

Objective

Low socioeconomic position (SEP) has been linked to an increased risk of dementia and cognitive decline. However, little is known about the association between SEP and morphologic brain changes in older age. This study examines the relationships between indicators of life-course SEP with both hippocampal volume (HcV) and HcV loss in a population-based cohort of 1328 older adults aged 65 to 80 years.

Methods

Multivariable linear regression models were used to estimate the associations of SEP with baseline HcV and the annual rate of HcV atrophy according to three life-course conceptual models: the sensitive/critical periods model (which explored SEP in specific periods: in childhood [using parental education], early adulthood [based on participants' education], and midlife [based on participants' socioprofessional group]); the accumulation-of-risk model (life-course cumulative SEP), and the social mobility model (life-course SEP trajectories).

Results

Participants with lower midlife SEP had smaller HcV (−0.08 cm3; 95% confidence interval, −0.15 to −0.01) and 0.17% (95% confidence interval, 0.04%–0.30%) faster hippocampal atrophy than participants with higher midlife SEP. Childhood and early adulthood SEPs were not related to hippocampal measures. The accumulation-of-risk and the social mobility models revealed that the accumulation of socioeconomic disadvantage and declining socioeconomic trajectories were related to faster hippocampal atrophy.

Conclusions

In this cohort of older adults, lower socioprofessional attainment in midlife and disadvantageous life-course socioeconomic position were associated with faster hippocampal atrophy, a cerebral change linked to cognitive disorders. Results support the hypothesized links between socioenvironmental exposures related to stress and/or cognitive enrichment and brain/cognitive reserve capacities.
Dimensions of Adversity, Physiological Reactivity, and Externalizing Psychopathology in Adolescence: Deprivation and Threat
Authors: Busso Daniel S. , McLaughlin Katie A. , Sheridan Margaret A.
Published: July 2016

Objective

Dysregulation of autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis function is a putative intermediate phenotype linking childhood adversity (CA) with later psychopathology. However, associations of CAs with autonomic nervous system and HPA-axis function vary widely across studies. Here, we test a novel conceptual model discriminating between distinct forms of CA (deprivation and threat) and examine their independent associations with physiological reactivity and psychopathology.

Methods

Adolescents (N = 169; mean [SD] age, 14.9 [1.4] years) with a range of interpersonal violence (e.g., maltreatment, community violence) and poverty exposure participated in the Trier Social Stress test (TSST). During the TSST, electrocardiogram, impedance cardiograph, salivary cortisol, and dehydroepiandrosterone-sulfate data were collected. We compared the associations of poverty (an indicator of deprivation) and interpersonal violence (an indicator of threat) on sympathetic, parasympathetic, and HPA-axis reactivity to the TSST, and assessed whether these differences mediated the association of adversity with internalizing and externalizing symptoms.

Results

Exposure to poverty and interpersonal violence was associated with psychopathology. Interpersonal violence, adjusting for poverty, was associated with blunted sympathetic (b = 1.44, p = .050) and HPA-axis reactivity (b = −.09; p = .021). Blunted cortisol reactivity mediated the association of interpersonal violence with externalizing, but not internalizing, psychopathology. In contrast, poverty was not associated with physiological reactivity after adjusting for interpersonal violence.

Conclusions

We provide evidence for distinct neurobiological mechanisms through which adversity related to poverty and interpersonal violence is associated with psychopathology in adolescence. Distinguishing distinct pathways through which adversity influences mental health has implications for preventive interventions targeting youths exposed to childhood adversity.
Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging
Authors: Kiecolt-Glaser Janice K. , Wilson Stephanie J.
Published: July 2016

A meta-analysis published in this issue of Psychosomatic Medicine provides convincing evidence that certain psychiatric populations have shorter telomeres than nonpsychiatric controls, in accord with the strong evidence linking psychiatric disorders with premature mortality. After addressing the clinical significance of shorter telomeres, this editorial describes mechanistic pathways that lead to telomere shortening. Additionally, two other novel methods for measuring biological markers of accelerated aging are briefly discussed: DNA methylation and cellular senescence based on p16INK4a. These innovative approaches could be used to confirm and extend our understanding of psychiatric patients’ increased health and mortality risks.
Hyperpolarized Gas Magnetic Resonance Lung Imaging in Children and Young Adults
Authors: Flors Lucia , Mugler John P. , de Lange Eduard E. , Miller Grady W. , Mata Jaime F. , Tustison Nick , Ruset Iulian C. , Hersman F. William , Altes Talissa A.
Published: July 2016

The assessment of early pulmonary disease and its severity can be difficult in young children, as procedures such as spirometry cannot be performed on them. Computed tomography provides detailed structural images of the pulmonary parenchyma, but its major drawback is that the patient is exposed to ionizing radiation. In this context, magnetic resonance imaging (MRI) is a promising technique for the evaluation of pediatric lung disease, especially when serial imaging is needed. Traditionally, MRI played a small role in evaluating the pulmonary parenchyma. Because of its low proton density, the lungs display low signal intensity on conventional proton-based MRI. Hyperpolarized (HP) gases are inhaled contrast agents with an excellent safety profile and provide high signal within the lung, allowing for high temporal and spatial resolution imaging of the lung airspaces. Besides morphologic information, HP MR images also offer valuable information about pulmonary physiology. HP gas MRI has already made new contributions to the understanding of pediatric lung diseases and may become a clinically useful tool. In this article, we discuss the HP gas MRI technique, special considerations that need to be made when imaging children, and the role of MRI in 2 of the most common chronic pediatric lung diseases, asthma and cystic fibrosis. We also will discuss how HP gas MRI may be used to evaluate normal lung growth and development and the alterations occurring in chronic lung disease of prematurity and in patients with a congenital diaphragmatic hernia.
Anastomotic Airway Complications After Lung Transplant
Authors: Luecke Kyle , Trujillo Camilo , Ford Jonathan , Decker Summer , Pelaez Andres , Hazelton Todd R. , Rojas Carlos A.
Published: July 2016

The purpose of this article is to review the normal appearance and common complications of the airway anastomosis in lung transplant patients with emphasis on computed tomography images with bronchoscopic correlation. The spectrum of complications will be presented as early (<1 mo after transplant) or late (>1 mo). Variations in surgical technique as well as presentation and management options for airway complications will also be discussed.
UCP2 Expression Is Increased in Pancreas From Brain-Dead Donors and Involved in Cytokine-Induced β Cells Apoptosis
Authors: Brondani Leticia A. , Rech Tatiana H. , Boelter Gabriela , Bauer Andrea C. , Leitão Cristiane B. , Eizirik Décio L. , Crispim Daisy
Published: July 2016

Background

Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial.

Methods

We have presently performed a case-control study to assess UCP2 expression in pancreas from BD donors (cases) and subjects who underwent pancreatectomy (controls). We next investigated the role of Ucp2 in cytokine-induced apoptosis of rat insulin-producing INS-1E cells.

Results

UCP2 gene expression was higher in pancreas from BD donors compared with controls (1.73 ± 0.93 vs 0.75 ± 0.66; fold change, P < 0.05). Ucp2 knockdown (80% at the protein and messenger RNA levels) reduced by 30% cytokine-induced apoptosis and nitric oxide production in INS-1E cells. This protection was associated with decreased expression of cleaved (activated) caspases 9 and 3, suggesting that Ucp2 knockdown interferes with cytokine triggering of the intrinsic apoptotic pathway. Moreover, both messenger RNA and protein concentrations of the antiapoptotic protein Bcl-2 were increased after Ucp2 knockdown in INS-1E cells.

Conclusions

These data suggest that UCP2 has an apoptotic effect in β cells via regulation of the intrinsic pathway of apoptosis.
Safety and Efficacy of Adjunctive Θ Burst Repetitive Transcranial Magnetic Stimulation to Right Inferior Parietal Lobule in Schizophrenia Patients With First-Rank Symptoms
Authors: Tikka Sai Krishna , Nizamie S. Haque , Venkatesh Babu G.M. , Aggarwal Nidhi , Das Archana Kumari , Goyal Nishant
Published: July 2016

Background

First-rank symptoms (FRS) in schizophrenia have been found to be associated with various cognitive and biological markers. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate such factors. We hypothesized that rTMS adjunctive to antipsychotics will be safe and effective in treatment of FRS in schizophrenia.

Methods

Schizophrenia patients with FRS randomly received either active or sham-magnetic resonance imaging navigated continuous Θ burst stimulation (cTBS)-rTMS to right inferior parietal lobule for 2 weeks; assessments were repeated. While primary outcome variables were safety profile, FRS and overall psychopathology; secondary outcomes were γ oscillatory activity, brain-derived neurotrophic factor levels, and self-monitoring function.

Results

No significant adverse events were reported in either group. None of the outcome measures showed sufficient power on the time by group analysis.

Conclusions

This study fails to demonstrate whether or not adjunctive cTBS to right inferior parietal lobule could significantly alleviate FRS. We also fail to provide evidence for whether this protocol has any effect on brain-derived neurotrophic factor levels, self-monitoring function, and right hemispheric γ oscillations.
Treatment of Severe Self-Injurious Behavior in Autism Spectrum Disorder by Neuromodulation
Authors: D'Agati Douglas , Chang Andrew D. , Wachtel Lee E. , Reti Irving M.
Published: July 2016

An increasing number of case reports and series document the safe and effective use of electroconvulsive therapy (ECT) in children, adolescents, and young adults with autism spectrum disorder who engage in severe, intractable, repetitive self-injurious behavior (SIB) without environmental or operant function. Although the treatment is very effective for such patients, they typically remain highly dependent on frequent maintenance ECT (M-ECT) to maintain suppression of the SIB achieved during the acute course. Some patients receive M-ECT as frequently as once every 5 days. Such a regimen is quite burdensome for the patient and the patient's family, and the long-term effects of such regimens, starting as early as childhood, are unknown. In this review, we explore the expanding literature supporting the use of ECT for suppressing severe SIB associated with autism spectrum disorder. We also focus on the possible development of alternate nonconvulsive focal forms of brain stimulation, which might replace frequent M-ECT or reduce how frequently a patient needs to receive it. Although there are scarce clinical data currently available supporting these latter treatments, future studies are clearly indicated.
3D sorghum reconstructions from depth images enable identification of quantitative trait loci regulating shoot architecture
Authors: McCormick Ryan F. , Truong Sandra K. , Mullet John E.
Published: July 2016

Dissecting the genetic basis of complex traits is aided by frequent and non-destructive measurements. Advances in range imaging technologies enable the rapid acquisition of three-dimensional (3D) data from an imaged scene. A depth camera was used to acquire images ofSorghum bicolor, an important grain, forage, and bioenergy crop, at multiple developmental timepoints from a greenhouse-grown recombinant inbred line population. A semi-automated software pipeline was developed and used to generate segmented, 3D plant reconstructions from the images. Automated measurements made from 3D plant reconstructions identified quantitative trait loci (QTL) for standard measures of shoot architecture such as shoot height, leaf angle and leaf length, and for novel composite traits such as shoot compactness. The phenotypic variability associated with some of the QTL displayed differences in temporal prevalence; for example, alleles closely linked with the sorghumDwarf3gene, an auxin transporter and pleiotropic regulator of both leaf inclination angle and shoot height, influence leaf angle prior to an effect on shoot height. Furthermore, variability in composite phenotypes that measure overall shoot architecture, such as shoot compactness, is regulated by loci underlying component phenotypes like leaf angle. As such, depth imaging is an economical and rapid method to acquire shoot architecture phenotypes in agriculturally important plants like sorghum to study the genetic basis of complex traits.
Zika virus may not be alone: proteomics associates a bovine-like viral diarrhea virus to microcephaly
Authors: Nogueira Fabio CS , Velasquez Erika , Melo Adriana SO , Domont Gilberto B , Sawa Akira
Published: July 2016

One Sentence Summary

Proteomics analysis lead us to suspect the presence of a Bovine-like viral diarrhea virus (BVDV-like) in the brain tissue of fetuses bearing microcephaly during the outbreak in Paraiba State, Brazil, 2015.

No direct experimental causal evidence confirms that the Zika virus is the sole etiological agent responsible for the development of brain malformations in human fetuses during pregnancy. We used a discovery-driven approach to analyze protein extracts of three Zika positive brains. Shotgun mass spectrometry (MS) proteomics did not identify any Zika protein in all samples. However, MS detected the presence of peptide(s) from the polyprotein of a Bovine-like viral diarrhea virus (BVDV-like) in Zika-positive brains. These results indicate that Zika virus may not be, per se, the only etiological agent responsible for microcephaly and suggests that discovery-driven approaches play an essential role in the screening of fluids or tissues for virus or other etiological agents.
The Forest, the Trees, and the Phylo-diversity Jungle
Authors: Mazel Florent , Tucker Caroline M. , Cadotte Marc W. , Carvalho Silvia B. , Davies T. Jonathan , Fritz Susanne A. , Grenyer Rich , Helmus Matthew R. , Mooers Arne Ø. , Pavoine Sandrine , Purschke Oliver , Rosauer Dan. F. , Winter Marten
Published: July 2016

The joint use of phylogenetic trees and ecological data has proven useful for many aspects of ecology. However, there are a multitude of phylo-diversity metrics with complex interdependencies and mathematical redundancies (the so-called ‘jungle’ of metrics). Several recentpapers have been trying to ‘map’ this jungle but appear at a first glance to contradict each other. We suggest that these contradictory results are in fact complementary and reflect two approaches to understand diversity metrics: the first focuses on general mathematical properties,the second focuses on assessing metric performance in relation to particular questions.In this manuscript, we discuss the complementarity of the two approaches and in particular how recent papers fit into this categorisation.
Detecting the impact of temperature on transmission of Zika, dengue and chikungunya using mechanistic models
Authors: Mordecai Erin A. , Cohen Jeremy M. , Evans Michelle V. , Gudapati Prithvi , Johnson Leah R. , Lippi Catherine A. , Miazgowicz Kerri , Murdock Courtney C. , Rohr Jason R. , Ryan Sadie J. , Savage Van , Shocket Marta S. , Ibarra Anna Stewart , Thomas Matthew B. , Weikel Daniel P.
Published: July 2016

Recent epidemics of Zika, dengue, and chikungunya have heightened the need to understand the seasonal and geographic range of transmission byAedes aegyptiandAe. albopictusmosquitoes. We use mechanistic transmission models to derive predictions for how the probability and magnitude of transmission for Zika, chikungunya, and dengue change with mean temperature, and we show that these predictions are well matched by human case data. Across all three viruses, models and human case data both show that transmission occurs between 18-34°C with maximal transmission occurring in a range from 26-29°C. Controlling for population size and two socioeconomic factors, temperature-dependent transmission based on our mechanistic model is an important predictor of human transmission occurrence and incidence. Risk maps indicate that tropical and subtropical regions are suitable for extended seasonal or year-round transmission, but transmission in temperate areas is limited to at most three months per year even if vectors are present. Such brief transmission windows limit the likelihood of major epidemics following disease introduction in temperate zones.

Author Summary

Understanding the drivers of recent Zika, dengue, and chikungunya epidemics is a major public health priority. Temperature may play an important role because it affects mosquito transmission, affecting mosquito development, survival, reproduction, and biting rates as well as the rate at which they acquire and transmit viruses. Here, we measure the impact of temperature on transmission by two of the most common mosquito vector species for these viruses,Aedes aegyptiandAe. albopictus. We integrate data from several laboratory experiments into a mathematical model of temperature-dependent transmission, and find that transmission peaks at 26-29°C and can occur between 18-34°C. Statistically comparing model predictions with recent observed human cases of dengue, chikungunya, and Zika across the Americas suggests an important role for temperature, and supports model predictions. Using the model, we predict that most of the tropics and subtropics are suitable for transmission in many or all months of the year, but that temperate areas like most of the United States are only suitable for transmission for a few months during the summer (even if the mosquito vector is present).
The metabolic profile of lag and exponential phases ofSaccharomyces cerevisiaegrowth changes continuously
Authors: Bento Rafael N. , Aradhya Miguel A. , Semedo Valdir A. R. , Bernardes Carlos E. S. , Piedade Manuel E. M. , Antunes Fernando
Published: July 2016

Cellular growth is usually separated in well-defined phases. For microorganism likeSaccharomyces cerevisiae,two phases usually defined are (1) a lag phase, in which no growth is observed and cells adapt to a new environment, followed by (2) an exponential phase, in which rapid proliferation occurs. Here we investigate whether these well-defined phases are uniform. By using flow-microcalorimetry, we found that the metabolic profile of the culture is continuously changing, both in the lag and exponential phases of growth. Along the lag phase there is a continuous increase in the energy that is dissipated irreversibly as heat, while in the exponential phase the opposite occurs. We also confirm recent observations that the oxidative component of metabolism decreases along the exponential phase. Interestingly, nutrient limitation further decreases the amount of energy that is dissipated irreversibly. Altogether, this points to a picture in which cells respond rapidly to minute environmental changes by adjusting their metabolic profile.
MIGS: Methylation Interpolated Gene Signatures Determine Associations Between Differential Methylation and Gene Expression
Authors: Schlosberg Christopher E , VanderKraats Nathan D , Edwards John R
Published: July 2016

A large number of genomic studies are underway to determine which genes are abnormally regulated by methylation in disease. However, our understanding of how disease-specific methylation changes potentially affect expression is poorly understood. We need better tools to explain specific variation in methylation that potentially affects gene expression in clinical sequencing. We have developed a model, Methylation Interpolated Gene Signatures (MIGS), that captures the complexity of DNA methylation changes around a gene promoter. Using data from the Roadmap Epigenomics Project, we show that MIGS significantly outperforms current methods to use methylation data to predict differential expression. We find that methylation changes at the TSS and downstream ~2kb are most predictive of expression change. MIGS will be an invaluable tool to analyze genome-wide methylation data as MIGS produces a longer and more accurate list of genes with methylation-associated expression changes.
Falco: A quick and flexible single-cell RNA-seq processing framework on the cloud
Authors: Yang Andrian , Troup Michael , Lin Peijie , Ho Joshua W. K.
Published: July 2016

Single-cell RNA-seq (scRNA-seq) is increasingly used in a range of biomedical studies. Nonetheless, current RNA-seq analysis tools are not specifically designed to efficiently process scRNA-seq data due to their limited scalability. Here we introduce Falco, a cloud-based framework to enable paralellisation of existing RNA-seq processing pipelines using big data technologies of Apache Hadoop and Apache Spark for performing massively parallel analysis of large scale transcriptomic data. Using two public scRNA-seq data sets and two popular RNA-seq alignment/feature quantification pipelines, we show that the same processing pipeline runs 2.6 – 145.4 times faster using Falco than running on a highly optimised single node analysis. Falco also allows user to the utilise low-cost spot instances of Amazon Web Services (AWS), providing a 65% reduction in cost of analysis.

Availability

Falco is available via a GNU General Public License athttps://github.com/VCCRI/Falco/

Contact

j.ho@victorchang.edu.au

Supplementary information

Supplementary data are available atBioRXivonline.
Metabolic complementation in bacterial communities: necessary conditions and optimality
Authors: Mori Matteo , Ponce-de-León Miguel , Peretó Juli , Montero Francisco Montero
Published: July 2016

Bacterial communities may display metabolic complementation, in which different members of the association partially contribute to the same biosynthetic pathway. In this way, the end product of the pathway is synthesized by the community as a whole. However, the emergence and the benefits of such complementation are poorly understood. Herein we present a simple model to analyze the metabolic interactions among bacteria, including the host in the case of endosymbiotic bacteria. The model considers two cell populations, with both cell types encoding for the same linear biosynthetic pathway. We have found that, for metabolic complementation to emerge as an optimal strategy, both product inhibition and large permeabilities are needed. In the light of these results, we then consider the patterns found in the case of tryptophan biosynthesis in the endosymbiont consortium hosted by the aphidCinara cedri.Using in-silico computed physicochemical properties of metabolites of this and other biosynthetic pathways, we verified that the splitting point of the pathway corresponds to themost permeable intermediate.
Antibody-Based Affinity Cryo-Electron Microscopy at 2.6 Å Resolution
Authors: Yu Guimei , Li Kunpeng , Huang Pengwei , Jiang Xi , Jiang Wen
Published: July 2016

The affinity cryo-electron microscopy (cryo-EM) approach has been explored in recent years to simplify and improve the sample preparation for cryo-EM. Despite the demonstrated successes for low-concentration and unpurified specimens, the lack of near-atomic structures using this approach has led to a common perception of affinity cryo-EM as a niche technique incapable of reaching high resolutions. Here, we report a ~2.6 Å structure solved using the antibody-based affinity grid approach with a Tulane virus sample of low concentration. This is the first near-atomic structure solved using the affinity cryo-EM approach. Quantitative analyses of the structure indicate data and reconstruction quality comparable to conventional grid preparation method using samples at high concentration. With the shifting of bottlenecks of cryo-EM structural studies to sample grid preparation, our demonstration of the sub-3 Å capability of affinity cryo-EM approach indicates its potential in revolutionizing cryo-EM sample preparation for a broader spectrum of specimens.
Functional genetic characterization by CRISPR-Cas9 of two enhancers ofFOXP2in a child with speech and language impairment
Authors: Torres-Ruiz R. , Benitez-Burraco A. , Martínez-Lage M. , Rodríguez-Perales S. , García-Bellido P.
Published: July 2016

Mutations in the coding region ofFOXP2are known to cause speech and language impairment. Microdeletions involving the region downstream the gene have been also associated to speech and cognitive deficits. We recently described a girl harbouring a complex chromosomal rearrangement with one breakpoint downstream the gene that might affect her speech and cognitive abilities via physical separation of distant regulatory DNA elements. In this study, we have used highly efficient targeted chromosomal deletions induced by the CRISPR/Cas9 genome editing tool to demonstrate the functionality of two enhancers, FOXP2-Eproximaland FOXP2-Edistal, located in the intergenic region betweenFOXP2and its adjacentMDFICgene. Deletion of any of these two functional enhancers in the neuroblastomic cell line SK-N-MC downregulatesFOXP2and decreases FOXP2 protein levels, conversely it upregulatesMDFICand increases MDFIC protein levels. This suggests that both regulatory elements may be shared betweenFOXP2andMDFIC. We expect these findings contribute to a deeper understanding of howFOXP2andMDFICare regulated to pace neuronal development supporting speech and language.
Transport efficiency of membrane-anchored kinesin-1 motors depends on motor density and diffusivity
Authors: Grover Rahul , Fischer Janine , Schwarz Friedrich W. , Walter Wilhelm J. , Schwille Petra , Diez Stefan
Published: July 2016

In eukaryotic cells, membranous vesicles and organelles are transported by ensembles of motor proteins. These motors, such as kinesin-1, have been well characterizedin vitroas single molecules or as ensembles rigidly attached to non-biological substrates. However, the collective transport by membrane-anchored motors, i.e. motors attached to a fluid lipid bilayer, is poorly understood. Here, we investigate the influence of motors anchorage to a lipid bilayer on the collective transport characteristics. We reconstituted ‘membrane-anchored’ gliding motility assays using truncated kinesin-1 motors with a streptavidin-binding-peptide tag that can attach to streptavidin-loaded, supported lipid bilayers. We found that the diffusing kinesin-1 motors propelled the microtubules in presence of ATP. Notably, we found the gliding velocity of the microtubules to be strongly dependent on the number of motors and their diffusivity in the lipid bilayer. The microtubule gliding velocity increased with increasing motor density and membrane viscosity, reaching up to the stepping velocity of single-motors. This finding is in contrast to conventional gliding motility assays where the density of surface-immobilized kinesin-1 motors does not influence the microtubule velocity over a wide range. We reason, that the transport efficiency of membrane-anchored motors is reduced because of their slippage in the lipid bilayer, an effect which we directly observed using singlemolecule fluorescence microscopy. Our results illustrate the importance of the motor-cargo coupling, which potentially provides cells with an additional means of regulating the efficiency of cargo transport.
Stimulant drug effects on touchscreen automated paired-associates learning (PAL) in rats
Authors: Roschlau Corinna , Votteler Angeline , Hauber Wolfgang
Published: July 2016

Here we tested in rats effects of the procognitive drugs modafinil and methylphenidate on post-acquisition performance in an object–location paired-associates learning (PAL) task. Modafinil (32; 64 mg/kg) was without effect, while higher (9 mg/kg) but not lower (4.5 mg/kg) doses of methylphenidate impaired PAL performance. Likewise, higher but not lower doses of amphetamine (0.4; 0.8 mg/kg) and MK-801 (0.08; 0.12 mg/kg) decreased PAL performance. Impaired PAL performance induced by methylphenidate, amphetamine, and MK801 most likely reflects compromised cognitive function, e.g., retrieval of learned paired associates. Our data suggest that stimulant drugs such as methylphenidate and modafinil might not facilitate performance in hippocampus-related cognitive tasks.
Voluntary running depreciates the requirement of Ca2+-stimulated cAMP signaling in synaptic potentiation and memory formation
Authors: Zheng Fei , Zhang Ming , Ding Qi , Sethna Ferzin , Yan Lily , Moon Changjong , Yang Miyoung , Wang Hongbing
Published: July 2016

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term potentiation (LTP) and memory formation in mice lacking type 1 adenylyl cyclase (AC1), a neurospecific synaptic enzyme that contributes to Ca2+-stimulated cAMP production. Following 1 mo of voluntary running-wheel exercise, the impaired LTP and object recognition memory in AC1 knockout (KO) mice were significantly attenuated. Running up-regulated exon II mRNA level of BDNF (brain-derived neurotrophic factor), though it failed to increase exon I and IV mRNAs in the hippocampus of AC1 KO mice. Intrahippocampal infusion of recombinant BDNF was sufficient to rescue LTP and object recognition memory defects in AC1 KO mice. Therefore, voluntary running and exogenous BDNF application overcome the defective Ca2+-stimulated cAMP signaling. Our results also demonstrate that alteration in Ca2+-stimulated cAMP can affect the molecular outcome of physical exercise.
Surface expression of NMDA receptor changes during memory consolidation in the crabNeohelice granulata
Authors: Hepp Yanil , Salles Angeles , Carbo-Tano Martin , Pedreira Maria Eugenia , Freudenthal Ramiro
Published: July 2016

The aim of the present study was to analyze the surface expression of the NMDA-like receptors during the consolidation of contextual learning in the crabNeohelice granulata. Memory storage is based on alterations in the strength of synaptic connections between neurons. The glutamatergic synapses undergo various forms ofN-methyl-D aspartate receptor (NMDAR)-dependent changes in strength, a process that affects the abundance of other receptors at the synapse and underlies some forms of learning and memory. Here we propose a direct regulation of the NMDAR. Changes in NMDAR's functionality might be induced by the modification of the subunit's expression or cellular trafficking. This trafficking does not only include NMDAR's movement between synaptic and extra-synaptic localizations but also the cycling between intracellular compartments and the plasma membrane, a process called surface expression. Consolidation of contextual learning affects the surface expression of the receptor without affecting its general expression. The surface expression of the GluN1 subunit of the NMDAR is down-regulated immediately after training, up-regulated 3 h after training and returns to naïve and control levels 24 h after training. The changes in NMDAR surface expression observed in the central brain are not seen in the thoracic ganglion. A similar increment in surface expression of GluN1 in the central brain is observed 3 h after administration of the competitive GABAAreceptor antagonist, bicuculline. These consolidation changes are part of a plasticity event that first, during the down-regulation, stabilizes the trace and later, at 3-h post-training, changes the threshold for synapse activation.
Positivity effect specific to older adults with subclinical memory impairment
Authors: Leal Stephanie L. , Noche Jessica A. , Murray Elizabeth A. , Yassa Michael A.
Published: July 2016

Numerous studies have suggested that older adults preferentially remember positive information (“positivity effect”), however others have reported mixed results. One potential source of conflict is that aging is not a unitary phenomenon and individual differences exist. We modified a standard neuropsychological test to vary emotional content and tested memory at three time points (immediate/20 min/1 wk). Cognitively normal older adults were stratified into those with and without subclinical memory impairment. We found that the positivity effect was limited to those with subclinical memory impairment, suggesting that consideration of subclinical memory impairment is necessary for understanding age-related emotional memory alterations.
Inhibition of protein synthesis but not β-adrenergic receptors blocks reconsolidation of a cocaine-associated cue memory
Authors: Dunbar Amber B. , Taylor Jane R.
Published: July 2016

Previously consolidated memories have the potential to enter a state of lability upon memory recall, during which time the memory can be altered before undergoing an additional consolidation-like process and being stored again as a long-term memory. Blocking reconsolidation of aberrant memories has been proposed as a potential treatment for psychiatric disorders including addiction. Here we investigated of the effect of systemically administering the protein synthesis inhibitor cycloheximide or the β-adrenergic antagonist propranolol on reconsolidation. Rats were trained to self-administer cocaine, during which each lever press resulted in the presentation of a cue paired with an intravenous infusion of cocaine. After undergoing lever press extinction to reduce operant responding, the cue memory was reactivated and rats were administered systemic injections of propranolol, cycloheximide, or vehicle. Post-reactivation cycloheximide, but not propranolol, resulted in a reactivation-dependent decrease in cue-induced reinstatement, indicative of reconsolidation blockade by protein synthesis inhibition. The present data indicate that systemically targeting protein synthesis as opposed to the β-adrenergic system may more effectively attenuate the reconsolidation of a drug-related memory and decrease drug-seeking behavior.
Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior
Authors: Kim Seonil , Pick Joseph E. , Abera Sinedu , Khatri Latika , Ferreira Danielle D.P. , Sathler Matheus F. , Morison Sage L. , Hofmann Franz , Ziff Edward B.
Published: July 2016

Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO hippocampus is increased as a functional compensation for gene deletion, while such compensation is absent in the prefrontal cortex. Thus, there are brain region-specific effects of cGKII KO on AMPAR trafficking, which could affect animal behavior. Here, we show that GluA1 phosphorylation levels differ in various brain regions, and specific behaviors are altered according to region-specific changes in GluA1 phosphorylation. Moreover, we identified distinct regulations of phosphatases in different brain regions, leading to regional heterogeneity of GluA1 phosphorylation in the KO brain. Our work demonstrates region-specific changes in GluA1 phosphorylation in cGKII KO mice and corresponding effects on cognitive performance. We also reveal distinct regulation of phosphatases in different brain region in which region-specific effects of kinase gene KO arise and can selectively alter animal behavior.
How important is thermal expansion for predicting molecular crystal structures and thermochemistry at finite temperatures?
Authors: Heit Yonaton N. , Beran Gregory J. O.
Published: July 2016

Molecular crystals expand appreciably upon heating due to both zero-point and thermal vibrational motion, yet this expansion is often neglected in molecular crystal modeling studies. Here, a quasi-harmonic approximation is coupled with fragment-based hybrid many-body interaction calculations to predict thermal expansion and finite-temperature thermochemical properties in crystalline carbon dioxide, ice Ih, acetic acid and imidazole. Fragment-based second-order Möller–Plesset perturbation theory (MP2) and coupled cluster theory with singles, doubles and perturbative triples [CCSD(T)] predict the thermal expansion and the temperature dependence of the enthalpies, entropies and Gibbs free energies of sublimation in good agreement with experiment. The errors introduced by neglecting thermal expansion in the enthalpy and entropy cancel somewhat in the Gibbs free energy. The resulting ∼ 1–2 kJ mol−1errors in the free energy near room temperature are comparable to or smaller than the errors expected from the electronic structure treatment, but they may be sufficiently large to affect free-energy rankings among energetically close polymorphs.