bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the role of corticotropin releasing factor binding protein in alcohol consumption
Authors: Haass-Koffler C L , Henry A T , Melkus G , Simms J A , Naemmuddin M , Nielsen C K , Lasek A W , Magill M , Schwandt M L , Momenan R , Hodgkinson C A , Bartlett S E , Swift R M , Bonci A , Leggio L 
Published: November 2016

AbstractThe corticotropin releasing factor (CRF) exerts its effects by acting on its receptors and on the binding protein (CRFBP), and has been implicated in alcohol use disorder (AUD). Therefore, identification of the exact contribution of each protein that mediates CRF effects is necessary to design effective therapeutic strategies for AUD. A series ofin vitro/in vivoexperiments across different species were performed to define the biological discrete role of CRFBP in AUD. First, to establish the CRFBP role in receptor signaling, we developed a novel chimeric cell-based assay and showed that CFRBP full length can stably be expressed on the plasma membrane. We discovered that only CRFBP(10 kD) fragment is able to potentiate CRF-intracellular Ca2+release. We provide evidence thatCRHBPgene loss increased ethanol consumption in mice. Then, we demonstrate that selective reduction ofCRHBPexpression in the center nucleus of the amygdala (CeA) decreases ethanol consumption in ethanol-dependent rats. CRFBP amygdalar downregulation, however, does not attenuate yohimbine-induced ethanol self-administration. This effect was associated with decreased hemodynamic brain activity in the CRFBP-downregulated CeA and increased hemodynamic activity in the caudate putamen during yohimbine administration. Finally, in alcohol-dependent patients, genetic variants related to the CRFBP(10 kD) fragment were associated with greater risk for alcoholism and anxiety, while other genetic variants were associated with reduced risk for anxiety. Taken together, our data provide evidence that CRFBP may possess both inhibitory and excitatory roles and may represent a novel pharmacological target for the treatment of AUD.
Brain responses to biological motion predict treatment outcome in young children with autism
Authors: Yang D , Pelphrey K A , Sukhodolsky D G , Crowley M J , Dayan E , Dvornek N C , Venkataraman A , Duncan J , Staib L , Ventola P 
Published: November 2016

AbstractAutism spectrum disorders (ASDs) are common yet complex neurodevelopmental disorders, characterized by social, communication and behavioral deficits. Behavioral interventions have shown favorable results—however, the promise of precision medicine in ASD is hampered by a lack of sensitive, objective neurobiological markers (neurobiomarkers) to identify subgroups of young children likely to respond to specific treatments. Such neurobiomarkers are essential because early childhood provides a sensitive window of opportunity for intervention, while unsuccessful intervention is costly to children, families and society. In young children with ASD, we show that functional magnetic resonance imaging-based stratification neurobiomarkers accurately predict responses to an evidence-based behavioral treatment—pivotal response treatment. Neural predictors were identified in the pretreatment levels of activity in response to biological vs scrambled motion in the neural circuits that support social information processing (superior temporal sulcus, fusiform gyrus, amygdala, inferior parietal cortex and superior parietal lobule) and social motivation/reward (orbitofrontal cortex, insula, putamen, pallidum and ventral striatum). The predictive value of our findings for individual children with ASD was supported by a multivariate pattern analysis with cross validation. Predicting who will respond to a particular treatment for ASD, we believe the current findings mark the very first evidence of prediction/stratification biomarkers in young children with ASD. The implications of the findings are far reaching and should greatly accelerate progress toward more precise and effective treatments for core deficits in ASD.
Newer insights into the role of miRNA a tiny genetic tool in psychiatric disorders: focus on post-traumatic stress disorder
Authors: Giridharan V V , Thandavarayan R A , Fries G R , Walss-Bass C , Barichello T , Justice N J , Reddy M K , Quevedo J 
Published: November 2016

AbstractPost-traumatic stress disorder (PTSD) is a mental disorder occurring in about 2–9% of individuals after their exposure to life-threatening events, such as severe accidents, sexual abuse, combat or a natural catastrophe. Because PTSD patients are exposed to trauma, it is likely that epigenetic modifications have an important role in disease development and prognosis. For the past two decades, abnormal expression of the epigenetic regulators microRNAs (miRs) and miR-mediated gene regulation have been given importance in a variety of human diseases, such as cancer, heart disease and viral infection. Emerging evidence supports a role for miR dysregulation in psychiatric and neurological disorders, including schizophrenia, bipolar disorder, anxiety, major depressive disorder, autism spectrum disorder and Tourette’s syndrome. Recently mounting of evidence supports the role of miR both in preclinical and clinical settings of psychiatric disorders. Abnormalities in miR expression can fine-tune the expression of multiple genes within a biological network, suggesting that miR dysregulation may underlie many of the molecular changes observed in PTSD pathogenesis. This provides strong evidence that miR not only has a critical role in PTSD pathogenesis, but can also open up new avenues for the development of diagnostic tools and therapeutic targets for the PTSD phenotype. In this review, we revisit some of the recent evidence associated with miR and PTSD in preclinical and clinical settings. We also discuss the possible clinical applications and future use of miRs in PTSD therapy.
Evidence for impaired glucose metabolism in the striatum, obtained postmortem, from some subjects with schizophrenia
Authors: Dean B , Thomas N , Scarr E , Udawela M 
Published: November 2016

AbstractStudies using central nervous system tissue obtained postmortem suggest pathways involved in energy and metabolism contribute to the pathophysiology of schizophrenia; neuroimaging studies suggesting glucose metabolism is particularly affected in the striatum. To gain information on the status of pathways involved in glucose metabolism in the striatum, we measured levels of glucose, pyruvate, acetyl-CoA and lactate as well as the β subunit of pyruvate dehydrogenase, a rate limiting enzyme, in the postmortem tissue from subjects with schizophrenia and age/sex-matched controls. The subjects with schizophrenia were made up of two subgroups, which could be divided because they either had (muscarinic receptor deficit schizophrenia (MRDS)), or did not have (non-MRDS), a marked deficit in cortical muscarinic receptors. Compared to controls, levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=−20%) and levels of pyruvate (Δ mean=+47%) and lactate (Δ mean=+15%) were significantly higher in the striatum from subjects with schizophrenia. Notably, in subjects with non-MRDS, striatal levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=−29%), whereas levels of pyruvate (Δ mean=−66%), acetyl-CoA (Δ mean=−28%) and glucose (Δ mean=-27%) were higher, whereas levels of lactate (Δ mean=+17%) were higher in MRDS. Finally, discriminate analyses using levels the β subunit of pyruvate dehydrogenase and glucose, or better still, β subunit of pyruvate dehydrogenase and glucose in combination with pyruvate, lactate or acetyl-CoA could separate subjects with non-MRDS from controls with high levels of specificity (up to 93%) and selectivity (up to 91%). Our data show the benefit of being able to study defined subgroups within the syndrome of schizophrenia as such an approach has revealed that changes in glucose metabolism may be a significant contributor to the pathophysiology of non-MRDS.
Predictive dead time controller for GaN‐based boost converters
Authors: Schirone Luigi , Macellari Michele , Pellitteri Filippo 
Published: November 2016

A dynamic dead time controller is presented, specifically intended to operate in synchronous boost converters based on GaN field‐effect transistor switches. These transistors have a reduced stored charge with respect to silicon metal–oxide–semiconductor field‐effect transistors with similar breakdown voltage and series resistance, and can operate at higher frequencies with reduced switching losses. On the other hand, the voltage drop in reverse conduction is typically more than doubled with respect to silicon devices resulting in relevant power losses during the free‐wheeling phases. Therefore, dynamic control of dead time can be profitably applied even in converters operating in the tens of volts range. The device presented in this study controls the switching delays taking into account both variations of the fall/rise times and of the turn‐off/on delays, in order to keep dead time within a range of a few nanoseconds above its minimum value. A discrete‐component prototype was designed, built in a synchronous boost converter and extensively tested at 1–2 MHz switching frequency, in a range of operating parameters corresponding to significant variations of the switching times (currents in the 1–6 A range, output voltage up to 50 V). The prototype demonstrated the capability to match dead time to actual operating conditions with a smooth and fast transient response.
Gesundheitsbezogene Lebensqualität im Rahmen der frühen Nutzenbewertung von Arzneimitteln nach § 35a SGB V: Ein Endpunkt mit vielen Herausforderungen für alle beteiligten Akteure
Authors: Bender H. , Dintsios C.-M. 
Published: November 2016

ZusammenfassungAngesichts des wiederholten Einforderns von Ergebnissen zum Endpunkt gesundheitsbezogene Lebensqualität im Zuge der frühen Nutzenbewertung sowie der anhaltenden methodischen Diskussionen stellt sich die Frage, welche Geltung diese Zielgröße im bisherigen Verlauf erfahren hat. Um die Stellung der gesundheitsbezogenen Lebensqualität im Bewertungsprozess zu bestimmen, wurden die veröffentlichten Dokumente zu den ersten 90 Verfahren diesbezüglich akteursbezogen extrahiert und synoptisch bewertet. Die Erkenntnisse sind vielschichtig. Im Grundsatz zeigt sich die Schwierigkeit, eine qualitative Zielgröße zu quantifizieren und deren Wertigkeit zu verorten. Erkennbar ist, dass der Endpunkt gesundheitsbezogene Lebensqualität in einer Reihe von Verfahren a priori nicht erhoben wurde. Liegen hingegen Daten zur gesundheitsbezogenen Lebensqualität vor, so kann vielfach ein Zusatznutzen nicht abgeleitet werden. In den verbleibenden Fällen schließlich wird ein solcher in der Mehrzahl vom IQWiG bzw. G-BA nicht anerkannt. Die Einbeziehung der gesundheitsbezogenen Lebensqualität im Studiensetting scheint zuzunehmen, allerdings ist allzu häufig eine explorative Konzeptualisierung des Endpunktes auszumachen. Entsprechend heterogen stellt sich das vorgefundene Evidenzniveau dar. Neben nicht erreichten statistischen Signifikanzen für eine, einen Zusatznutzen begründende, Berücksichtigung benennen die Evaluationsberichte insbesondere diverse methodische Limitationen, die aus Sicht der Bewertungsinstanzen einen Ausschluss begründen. So werden etwa hohe Anteile fehlender Patientendaten oder Schwierigkeiten bei der Interpretierbarkeit der Messergebnisse angeführt. Hinsichtlich der dahinterstehenden Bewertungssystematiken zeigen sich allerdings Inkonsistenzen bei der Anwendung sowohl konzeptioneller als auch methodischer Standards. Um die Wertigkeit des Endpunktes gesundheitsbezogene Lebensqualität innerhalb der frühen Nutzenbewertung zu erhöhen, erscheint es notwendig, verlässliche (Mess-)Standards konsensuell zu etablierten. Zudem sollten die Wertungskriterien transparenter gemacht und eine Harmonisierung mit dem Zulassungsprozess zumindest für die Erstbewertung angestrebt werden.
Life cycle greenhouse gas emissions and freshwater consumption associated with Bakken tight oil
Authors: Laurenzi Ian J. , Bergerson Joule A. , Motazedi Kavan 
Published: November 2016

SignificanceThe growth of production from tight oil plays such as the Bakken and Eagle Ford has prompted public interest in understanding the greenhouse gas (GHG) emissions and freshwater consumption associated with these resources, specifically with regard to hydraulic fracturing and flaring. Therefore, we conducted a comprehensive life cycle assessment of Bakken crude, using thousands of data from XTO Energy and other Bakken operators, establishing robust estimates of the footprint of current production practices. We conclude that flaring and hydraulic fracturing have a small impact on the life cycle (well to wheel) GHG emissions associated with Bakken and that these GHG emissions are comparable to those of other crudes.
Origins of the current seventh cholera pandemic
Authors: Hu Dalong , Liu Bin , Feng Lu , Ding Peng , Guo Xi , Wang Min , Cao Boyang , Reeves Peter R. , Wang Lei 
Published: November 2016

SignificanceCholera, a major disease in human history, has terrorized the world through seven pandemics. The seventh pandemic started in Indonesia in 1961 and spread globally, currently infecting 3–5 million people annually. By combining all available historical records and genomic analysis of available preseventh pandemic and some early pandemic strains, we revealed the complex six-step evolution of the pandemic strain from its probable origin in South Asia to its nonpathogenic form in the Middle East in ∼1900 to Indonesia in ∼1925, where it evolved into a pandemic strain before becoming widespread in 1961. This pathway relates to human traffic routes, including the annual Hajj pilgrimage, and involved novel niches that provided gene sources and the driving forces for stepwise evolution.
DNA polymerase ζ limits chromosomal damage and promotes cell survival following aflatoxin exposure
Authors: Lin Ying-Chih , Owen Nichole , Minko Irina G. , Lange Sabine S. , Tomida Junya , Li Liang , Stone Michael P. , Wood Richard D. , McCullough Amanda K. , Lloyd R. Stephen 
Published: November 2016

Significance
Human dietary exposures to foods contaminated with fungi that synthesize aflatoxins present major health concerns and are associated with increased risk of hepatocellular carcinomas. Previous biochemical analyses revealed a prominent role for DNA polymerase ζ in replication bypass and mutagenesis of the long-lived aflatoxin DNA adduct. This investigation reveals an essential role for polymerase ζ in cell survival after aflatoxin exposure and that polymerase ζ limits aflatoxin-induced genomic instability and associated nuclear defects.
VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis
Authors: Licht Tamar , Rothe Gadiel , Kreisel Tirzah , Wolf Brachi , Benny Ofra , Rooney Alasdair G. , ffrench-Constant Charles , Enikolopov Grigori , Keshet Eli 
Published: November 2016

Significance
Generation of new neurons is maintained in the adult hippocampus throughout life. The process, which is driven by an exhaustible reservoir of neuronal stem cells (NSCs), greatly declines with age, however. We show that even a short, episodic exposure to the angiogenic factor VEGF and a resultant ramification/rejuvenation of the vasculature within the stem cell microenvironment (“niche”) is sufficient for neurogenesis to proceed at a markedly elevated rate for months later without accelerating the rate of NSC depletion. Importantly, this manipulation culminates in marked attenuation of age-dependent neurogenic decline. Long-term neurogenic enhancement via VEGF preconditioning was found to be associated with extensive NSC morphological remodeling resembling a “juvenile” pattern of NSC and blood vessel engagements.
Mapping membrane activity in undiscovered peptide sequence space using machine learning
Authors: Lee Ernest Y. , Fulan Benjamin M. , Wong Gerard C. L. , Ferguson Andrew L. 
Published: November 2016

Significance
We use machine learning on membrane-permeating ⍺-helical host defense peptides to study the nature of their functional commonality and sequence homology. Machine learning is combined with calibrating experiments to show that the metric in our support vector machine model correlates not with antimicrobial activity but with a peptide’s ability to generate the negative Gaussian membrane curvature necessary for membrane permeation. Moreover, we use the classifier reflexively to map the undiscovered sequence space of antimicrobial peptides and identify taxonomies of peptides with similar topological membrane remodeling activity, including endogenous neuropeptides, viral fusion proteins, topogenic peptides, and amyloids.
Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells
Authors: Hurton Lenka V. , Singh Harjeet , Najjar Amer M. , Switzer Kirsten C. , Mi Tiejuan , Maiti Sourindra , Olivares Simon , Rabinovich Brian , Huls Helen , Forget Marie-Andrée , Datar Vrushali , Kebriaei Partow , Lee Dean A. , Champlin Richard E. , Cooper Laurence J. N. 
Published: November 2016

Significance
We describe an approach based on cytokine therapeutics to enhance the persistence and effectiveness of T-cell–based immunotherapies using chimeric antigen receptors (CARs). This strategy is effective without the use of high-dose exogenous cytokines that are typically associated with toxicities. Moreover, we report that the persistence of the least differentiated memory T cell, the T-memory stem cell, was promoted by signaling induced by a membrane-bound chimeric IL-15 cytokine-fusion molecule. These findings may contribute to improving the safety and therapeutic efficacy of CAR-based immunotherapies of patients with advanced cancer.
Amyloid fibrils from the N-terminal prion protein fragment are infectious
Authors: Choi Jin-Kyu , Cali Ignazio , Surewicz Krystyna , Kong Qingzhong , Gambetti Pierluigi , Surewicz Witold K. 
Published: November 2016

Significance
Prion diseases are a group of transmissible neurodegenerative disorders. The protein-only hypothesis asserts that transmission of these diseases does not require nucleic acids and that a misfolded, aggregated form of the prion protein represents a self-perpetuating infectious agent. Even though this model is supported by a large body of experimental data, there is a dispute regarding the role of specific cofactors in prion infectivity as well as the structural basis of prion formation. In this work, we show that structurally well-characterized amyloid fibrils generated from bacterially expressed prion protein fragment 23-144 cause prion disease in transgenic and wild-type mice, demonstrating that cofactors are not obligatory for prion formation and providing insight into the structural basis of prion propagation.
Heparanase is required for activation and function of macrophages
Authors: Gutter-Kapon Lilach , Alishekevitz Dror , Shaked Yuval , Li Jin-Ping , Aronheim Ami , Ilan Neta , Vlodavsky Israel 
Published: November 2016

Significance
The tumor microenvironment is now considered to play a major role in cancer growth and metastasis. Heparanase is the only enzyme in mammals capable of cleaving heparan sulfate, an activity that is highly implicated in tumor growth, metastasis, and inflammation. Here we provide evidence that heparanase is critically required for the activation and function of macrophages, an important constituent of the tumor microenvironment. Mechanistically, we describe a linear cascade by which heparanase activates Erk, p38, and JNK signaling in macrophages, leading to increased c-Fos levels and induction of cytokine expression in a manner that apparently does not require heparanase enzymatic activity. These results identify heparanase as a key mediator of macrophage activation and function in tumorigenesis and cross-talk with the tumor microenvironment.
Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage
Authors: Hill Sarah J. , Mordes Daniel A. , Cameron Lisa A. , Neuberg Donna S. , Landini Serena , Eggan Kevin , Livingston David M. 
Published: November 2016

Significance
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which progressive dysfunction of motor neurons leads to paralysis and death. There is currently no known pathway of disease pathogenesis. However, many genes with varying functions have been linked to familial and sporadic forms of ALS suggesting multiple possible disease mechanisms. One set of gene products, including ALS-linked FUS and TDP43, functions in transcription and RNA processing. We find that defects in transcription due to loss of function of FUS or TDP43 can lead to DNA damage, including in primary human neuronal cells, and hypothesize that dysfunction in their RNA processing roles leads to DNA damage in motor neurons that, if incompletely resolved, could contribute to motor neuron death and ALS.
Phylogenetic approach to the evolution of color term systems
Authors: Haynie Hannah J. , Bowern Claire 
Published: November 2016

Significance
A major question in the study of both anthropology and cognitive science is why the world’s languages show recurrent similarities in color naming. Here we examine this inherently evolutionary question–the evolution of color systems in language–using phylogenetic methods. We track the evolution of color terms across a large language tree in order to trace the history of the systems. We provide further validation of phylogenetic approaches to culture, and provide an explicit history of color terms across a large language sample, the Pama-Nyungan languages of Australia. Our work is of relevance to anthropologists, psychologists, and linguists.
Burkina Faso: from Thomas Sankara to popular resistance
Authors: Zeilig Leo 
Published: November 2016

SUMMARY
Arguably the résistance populaire across Burkina Faso in September 2015 against the coup led by members of the old regime was as significant as the uprising that toppled Blaise Compaoré in October 2014. This Briefing attempts to unpick the significance and extent of the popular resistance.
Challenging the 4- to 5-minute Rule: From Perimortem Cesarean to Resuscitative Hysterotomy
Authors: Rose C.H. , Faksh A. , Traynor K.D. , Cabrera D. , Arendt K.W. , Brost B.C. 
Published: November 2016

(Am J Obstet Gynecol 2015;213(5):653–656. 653.e1)
About 1/12,500 deliveries are complicated by antepartum maternal cardiac arrest, causative factors of which include hemorrhage, amniotic fluid embolism, heart failure, sepsis, anesthetic complications, and trauma. The maternal survival rate ranges from 17% to 59% and fetal survival rates from 61% to 80%. This article is a review of current practices for maternal cardiopulmonary arrest (MCPA) management and also proposes a maternofetal management strategy that differs from the current 4 to 5 minute rule for perimortem cesarean delivery (PMCD).
The Placenta is the Center of the Chronic Disease Universe
Authors: Thornburg K.L. , Marshall N. 
Published: November 2016

(Am J Obstet Gynecol 2015;213(suppl):S14–S20)
This review article explores the potential role of the placenta in the development of chronic diseases later in life. It discusses studies reporting an inverse relationship between birthweight and chronic disease, leading to a better understanding of health and longevity in offspring. Researchers have long studied the mechanism by which compromised fetal development leads to the onset of certain diseases in adulthood. They refer to this as process as “programming.” Research has shown that there are links between early life development and the incidence of obesity, diabetes, and heart disease. One study by Barker and colleagues estimated that diabetes could be reduced by approximately 60% in a generation if children were born at the lowest risk birthweight and did not cross body mass index percentiles in childhood.