bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of objectively assessed 24-hour motor activity patterns as a potential marker for bipolar I disorder: results of a community-based family study
Authors: Shou H , Cui L , Hickie I , Lameira D , Lamers F , Zhang J , Crainiceanu C , Zipunnikov V , Merikangas K R 
Published: August 2017

AbstractThere has been a growing number of studies that have employed actigraphy to investigate differences in motor activity in mood disorders. In general, these studies have shown that people with bipolar disorders (BPDs) tend to exhibit greater variability and less daytime motor activity than controls. The goal of this study was to examine whether patterns of motor activity differ in euthymic individuals across the full range of mood disorder subtypes (Bipolar I (BPI), Bipolar II (BPII) and major depression (MDD)) compared with unaffected controls in a community-based family study of mood spectrum disorders. Minute-to-minute activity counts derived from actigraphy were collected over a 2-week period for each participant. Prospective assessments of the level, timing and day-to-day variability of physical activity measures were compared across diagnostic groups after controlling for a comprehensive list of potential confounding factors. After adjusting for the effects of age, sex, body mass index (BMI) and medication use, the BPI group had lower median activity intensity levels across the second half of the day and greater variability in the afternoon compared with controls. Those with a history of BPII had increased variability during the night time compared with controls, indicating poorer sleep quality. No differences were found in the average intensity, variability or timing of activity in comparisons between other mood disorder subgroups and controls. Findings confirm evidence from previous studies that BPI may be a manifestation of a rhythm disturbance that is most prominent during the second half of the day. The present study is the largest study to date that included the full range of mood disorder subgroups in a nonclinical sample that increases the generalizability of our findings to the general community. The manifestations of activity patterns outside of acute episodes add to the accumulating evidence that dysregulation of patterns of activity may constitute a potential biomarker for BPD.
Neuregulin signaling pathway in smoking behavior
Authors: Gupta R , Qaiser B , He L , Hiekkalinna T S , Zheutlin A B , Therman S , Ollikainen M , Ripatti S , Perola M , Salomaa V , Milani L , Cannon T D , Madden P A F , Korhonen T , Kaprio J , Loukola A 
Published: August 2017

AbstractUnderstanding molecular processes that link comorbid traits such as addictions and mental disorders can provide novel therapeutic targets. Neuregulin signaling pathway (NSP) has previously been implicated in schizophrenia, a neurodevelopmental disorder with high comorbidity to smoking. Using a Finnish twin family sample, we have previously detected association between nicotine dependence andERBB4(a neuregulin receptor), and linkage for smoking initiation at theERBB4locus on 2q33. Further,Neuregulin3has recently been shown to associate with nicotine withdrawal in a behavioral mouse model. In this study, we scrutinized association and linkage between 15 036 common, low frequency and rare genetic variants in 10 NSP genes and phenotypes encompassing smoking and alcohol use. Using the Finnish twin family sample (N=1998 from 740 families), we detected 66 variants (representing 23 LD blocks) significantly associated (false discovery rateP<0.05) with smoking initiation, nicotine dependence and nicotine withdrawal. We comprehensively annotated the associated variants using expression (eQTL) and methylation quantitative trait loci (meQTL) analyses in a Finnish population sample. Among the 66 variants, we identified 25 eQTLs (inNRG1andERBB4), 22 meQTLs (inNRG3,ERBB4andPSENEN), a missense variant inNRG1(rs113317778) and a splicing disruption variant inERBB4(rs13385826). Majority of the QTLs in blood were replicatedin silicousing publicly available databases, with additional QTLs observed in brain. In conclusion, our results support the involvement of NSP in smoking behavior but not in alcohol use and abuse, and disclose functional potential for 56 of the 66 associated single-nucleotide polymorphism.
Association of the serotonin transporter-linked polymorphic region genotype with lower bone mineral density
Authors: Lapid M I , Kung S , Frye M A , Biernacka J M , Geske J R , Drake M T , Jankowski M D , Clarke B L 
Published: August 2017

AbstractThe serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) S allele is linked to pathogenesis of depression and slower response to selective serotonin reuptake inhibitors (SSRIs); depression and SSRIs are independently associated with bone loss. We aimed to determine whether 5-HTTLPR was associated with bone loss. This cross-sectional study included psychiatric patients with both 5-HTTLPR analysis and bone mineral density (BMD) assessment (hip and spine Z-scores if age <50 years and T-scores if ⩾50 years). BMD association with 5-HTTLPR was evaluated under models with additive allele effects and dominant S allele effects using linear regression models. Patients were stratified by age (<50 and ⩾50 years) and sex. Of 3016 patients with 5-HTTLPR genotyping, 239 had BMD assessments. Among the younger patients, the S allele was associated with lower Z-scores at the hip (P=0.002, dominant S allele effects; P=0.004, additive allele effects) and spine (P=0.0006, dominant S allele effects; P=0.01, additive allele effects). In sex-stratified analyses, the association of the S allele with lower BMD in the younger patients was also significant in the subset of women (P⩽0.003 for both hip and spine BMD under the additive allele effect model). In the small group of men younger than 50 years, the S allele was marginally associated with higher spine BMD (P=0.05). BMD T-scores were not associated with 5-HTTLPR genotypes in patients 50 years or older. The 5-HTTLPR variants may modify serotonin effects on bone with sex-specific effects.
Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats
Authors: Noble L J , Gonzalez I J , Meruva V B , Callahan K A , Belfort B D , Ramanathan K R , Meyers E , Kilgard M P , Rennaker R L , McIntyre C K 
Published: August 2017

AbstractExposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.
Octave bandwidth in‐line rectangular waveguide‐to‐coaxial transition using oversized mode conversion
Authors: Cano J.L. , Mediavilla A. 
Published: August 2017

A very low‐loss in‐line rectangular waveguide‐to‐coaxial transition covering an octave bandwidth is presented. In order to obtain such frequency coverage, the transition employs oversized mode conversion, i.e. the rectangular waveguide dimensions are internally enlarged to modify the cavity cutoff frequency while obtaining good matching properties for a standard rectangular waveguide output port. A four‐step ridge transformer is included for the TE‐to‐TE10 mode conversion in the whole frequency range. The transition, completed with a commercial SMA connector for the coaxial port, exhibits a return loss of around 25 dB with 0.1 dB insertion loss when measured in back‐to‐back configuration in the 10–20 GHz frequency range. From these results, an input matching around 30 dB and an insertion loss around 0.05 dB for a stand‐alone transition can be inferred.
Sizing up the population of gamma-ray binaries
Authors: Dubus Guillaume , Guillard Nicolas , Petrucci Pierre-Olivier , Martin Pierrick 
Published: August 2017

Context.Gamma-ray binaries are thought to be composed of a young pulsar in orbit around a massive O or Be star with their gamma-ray emission powered by pulsar spin-down. The number of such systems in our Galaxy is not known.Aims.We aim to estimate the total number of gamma-ray binaries in our Galaxy and to evaluate the prospects for new detections in the GeV and TeV energy range, taking into account that their gamma-ray emission is modulated on the orbital period.Methods.We modelled the population of gamma-ray binaries and evaluated the fraction of detected systems in surveys with theFermi-LAT (GeV), H.E.S.S., HAWC and CTA (TeV) using observation-based and synthetic template light curves.Results.The detected fraction depends more on the orbit-average flux than on the light-curve shape. Our best estimate for the number of gamma-ray binaries is 101\hbox{$_{-52}^{+89}$} systems. A handful of discoveries are expected by pursuing theFermi-LAT survey. Discoveries in TeV surveys are less likely. However, this depends on the relative amounts of power emitted in GeV and TeV domains. There could be as many as ≈ 200 HESS J0632+057-like systems with a high ratio of TeV to GeV emission compared to other gamma-ray binaries. Statistics allow for as many as three discoveries in five years of HAWC observations and five discoveries in the first two years of the CTA Galactic Plane survey.Conclusions.We favour continuedFermi-LAT observations over ground-based TeV surveys to find new gamma-ray binaries. Gamma-ray observations are most sensitive to short orbital period systems with a high spin-down pulsar power. Radio pulsar surveys (SKA) are likely to be more efficient in detecting long orbital period systems, providing a complementary probe into the gamma-ray binary population.
Nitrile versus isonitrile adsorption at interstellar grain surfaces
Authors: Bertin M. , Doronin M. , Michaut X. , Philippe L. , Markovits A. , Fillion J.-H. , Pauzat F. , Ellinger Y. , Guillemin J.-C. 
Published: August 2017

Context. Almost 20% of the ~200 different species detected in the interstellar and circumstellar media present a carbon atom linked to nitrogen by a triple bond. Of these 37 molecules, 30 are nitrile R-CN compounds, the remaining 7 belonging to the isonitrile R-NC family. How these species behave in their interactions with the grain surfaces is still an open question.
Aims. In a previous work, we have investigated whether the difference between nitrile and isonitrile functional groups may induce differences in the adsorption energies of the related isomers at the surfaces of interstellar grains of various nature and morphologies. This study is a follow up of this work, where we focus on the adsorption on carbonaceous aromatic surfaces.
Methods. The question is addressed by means of a concerted experimental and theoretical approach of the adsorption energies of CH3CN and CH3NC on the surface of graphite (with and without surface defects). The experimental determination of the molecule and surface interaction energies is carried out using temperature-programmed desorption in an ultra-high vacuum between 70 and 160 K. Theoretically, the question is addressed using first-principle periodic density functional theory to represent the organised solid support.
Results. The adsorption energy of each compound is found to be very sensitive to the structural defects of the aromatic carbonaceous surface: these defects, expected to be present in a large numbers and great diversity on a realistic surface, significantly increase the average adsorption energies to more than 50% as compared to adsorption on perfect graphene planes. The most stable isomer (CH3CN) interacts more efficiently with the carbonaceous solid support than the higher energy isomer (CH3NC), however.
Reactions of Arynes Involving Transition-Metal Catalysis
Authors: Jiang Xuefeng , Feng Minghao 
Published: August 2017

Arynes are important building blocks for introducing aromatic rings into molecules and they are frequently utilized in syntheses. Historically, arynes were generated under harsh conditions and this limited their use. Arynes can now be generated under milder conditions, e.g. from 2-(trimethylsilyl)phenyl triflate, and utilized in transition-metal­ catalyzed reactions such as [2+2+2] reactions, insertion into σ-bonds, cascade cyclizations and C–H activation reactions. This short review focuses on transition-metal-catalyzed reactions relevant to aryne intermediates generated from 2-(trimethylsilyl)phenyl triflates and other aryne precursors.1	Introduction2	[2+2+2] Reactions3	Aryne Insertion into a σ-Bond4	Cascade Cyclizations5	C–H Activation6	Multicomponent Reactions (MCRs)7	Conclusion
Syntheses of Dimeric Securinega Alkaloids
Authors: Han Sunkyu , Jeon Sangbin , Park Joonoh 
Published: August 2017

The isolation of flueggenines A and B by Yue and co-workers in 2006 has triggered a burst of isolation reports of dimeric and oligomeric securinega alkaloid natural products. The compelling molecular structures of these compounds with various modes of connection between monomeric securinega units have posed intriguing challenges to the synthetic organic community. Herein, we have categorized high-order securinega alkaloids based on their biosynthetic mode of dimerization or oligomerization. We then have compiled all reported syntheses of dimeric securinega alkaloids based on our classification.1	Introduction2	Categorization of High-Order Securinega Alkaloid Natural Products3	Syntheses of Type I Dimeric Securinega Alkaloids4	Syntheses of Type II Dimeric Securinega Alkaloids5	Synthesis of Type III Dimeric Securinega Alkaloid6	Conclusion
Transition-Metal-Free Reactions Between Boronic Acids and N-Sulfonylhydrazones or Diazo Compounds: Reductive Coupling Processes and Beyond
Authors: Valdés Carlos , Paraja Miguel , Plaza Manuel 
Published: August 2017

The metal-free reaction between diazo compounds and boronic acids has been established in recent years as a powerful C(sp3)–C bond-forming reaction. This account covers the recent advances in this area. First, the various synthetic applications of reactions with N-sulfonylhydrazones as a convenient source of diazo compounds is discussed. These transformations can be regarded as reductive couplings of carbonyl compounds. Also covered is the incorporation of other mild sources of diazo compounds in these reactions: diazotization of amines and oxidation of hydrazones. Finally, the development of sequential and cascade processes is presented.1	Introduction2	Early Work: Reactions Between Alkylboranes and Diazo Compounds or N-Sulfonylhydrazones2.1	Reactions Between Alkylboranes and Diazo Compounds2.2	Reactions Between Alkylboranes and N-Sulfonylhydrazones3	Reactions of N-Sulfonylhydrazones and Diazo Compounds with Aryl and Alkylboronic Acids3.1	Reactions of Arylboroxines with Diazo Compounds3.2	Reductive Couplings of N-Sulfonylhydrazones with Aryl- and Alkylboronic Acids3.3	Three-Component Reactions Between α-Halotosylhydrazones, Boronic Acids and Indoles4	Reactions of N-Tosylhydrazones with Alkenylboronic Acids5	Synthesis of Allenes by Reactions with Alkynyl N-Nosylhydrazones6	Reactions with Diazo Compounds Generated by Diazotization of Primary Amines7	Reactions with Diazo Compounds Generated by Oxidation of ­Hydrazones8	Reactions with Trimethylsilyldiazomethane9	Cascade Cyclization Reactions with γ- and δ-Cyano-N-tosylhydrazones10	Summary and Outlook
Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction
Authors: Cintron-Colon Rigo , Sanchez-Alavez Manuel , Nguyen William , Mori Simone , Gonzalez-Rivera Ruben , Lien Tiffany , Bartfai Tamas , Aïd Saba , François Jean-Christophe , Holzenberger Martin , Conti Bruno 
Published: August 2017

Significance
Energy homeostasis is fundamental for the survival of living organisms and contributes to their health, longevity, and aging. When food resources are scarce, and during experimental calorie restriction, endothermic animals can lower their core body temperature. Here, we found that this response is regulated by the insulin-like growth factor 1 receptor. This demonstrates that the three main factors affecting aging and longevity (calorie restriction, reduction of the insulin-like growth factor 1 signaling, and lowered temperature) are components of the same pathway that modulates energy homeostasis. The finding also identifies body temperature reduction as a common determinant of the effects of both calorie restriction and reduced insulin-like growth factor 1 receptor signaling.
Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization
Authors: Hasegawa Eiichi , Inafuku Saori , Mulki Lama , Okunuki Yoko , Yanai Ryoji , Smith Kaylee E. , Kim Clifford B. , Klokman Garrett , Bielenberg Diane R. , Puli Narender , Falck John R. , Husain Deeba , Miller Joan W. , Edin Matthew L. , Zeldin Darryl C. , Lee Kin Sing Stephen , Hammock Bruce D. , Schunck Wolf-Hagen , Connor Kip M. 
Published: August 2017

Significance
Abnormal blood vessel growth occurs in many common diseases, from cancers and cardiovascular diseases to ocular conditions like age-related macular degeneration (AMD) and is thus a major target of many recent treatment approaches. Long-chain polyunsaturated fatty acids are of significant interest in this context, since bioactive lipid metabolites derived from this pathway have been shown to be potent regulators of inflammation and angiogenesis. Our study has identified key compounds of the cytochrome P450 metabolic pathway that are responsible for resolving abnormal vascular growth in AMD, which work in part by modulating the recruitment of inflammatory immune cells. We believe these findings have significant therapeutic implications not only for AMD but also for other inflammatory disorders.
Changes in human skull morphology across the agricultural transition are consistent with softer diets in preindustrial farming groups
Authors: Katz David C. , Grote Mark N. , Weaver Timothy D. 
Published: August 2017

SignificanceAgriculture changed not only human culture and lifeways, but human biology as well. Previous studies indicate that softer agricultural diets may have resulted in a less robust craniofacial morphology in early farmers. However, obtaining reliable estimates of worldwide subsistence effects has proved challenging. Here, we quantify changes in human skull shape and form across the agricultural transition at a global scale. Although modest, the effects are often reliably directional and most pronounced in craniofacial features that are directly involved in mastication.
DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease
Authors: Jeziorska Danuta M. , Murray Robert J. S. , De Gobbi Marco , Gaentzsch Ricarda , Garrick David , Ayyub Helena , Chen Taiping , Li En , Telenius Jelena , Lynch Magnus , Graham Bryony , Smith Andrew J. H. , Lund Jonathan N. , Hughes Jim R. , Higgs Douglas R. , Tufarelli Cristina 
Published: August 2017

Significance
The human genome contains ∼30,000 CpG islands (CGIs), long stretches (0.5–2 kb) of DNA with unusually elevated levels of CpG dinucleotides. Many occur at genes' promoters, and their DNA nearly always remains unmethylated. Conversely, intragenic CGIs are often, but not always, methylated, and thus inactive as internal promoters. The mechanisms underlying these contrasting patterns of CGI methylation are poorly understood. We show that methylation of intragenic CGIs is associated with transcription running across the island. Whether or not a particular intragenic CGI becomes methylated during development depends on its transcriptional activity relative to that of the gene within which it lies. Our findings explain how intragenic CGIs are epigenetically programmed in normal development and in human diseases, including malignancy.
Involvement of posttranscriptional regulation of
Clock
in the emergence of circadian clock oscillation during mouse development
Authors: Umemura Yasuhiro , Koike Nobuya , Ohashi Munehiro , Tsuchiya Yoshiki , Meng Qing Jun , Minami Yoichi , Hara Masayuki , Hisatomi Moe , Yagita Kazuhiro 
Published: August 2017

Significance
Circadian clocks reside in each cell level throughout the body in mammals. Intrinsic cellular circadian clocks develop cell autonomously during the cellular differentiation process. However, mechanisms controlling the emergence of cellular circadian clock oscillation in vivo are not fully understood. Here, we show that Dicer/Dgcr8-mediated posttranscriptional mechanisms control the CLOCK protein expression in both mouse fetal hearts and in vitro differentiating ES cells, which contributes to the emergence of circadian clock in mammalian cells. This event occurs after cell lineage determination into hearts or loss of pluripotent stem cell markers in differentiating ES cells, suggesting the cellular differentiation-coupled clock development may be conducted by a two-step program consisting of cellular differentiation and subsequent establishment of circadian transcriptional/translational feedback loops.
Asymmetries in behavioral and neural responses to spectral cues demonstrate the generality of auditory looming bias
Authors: Baumgartner Robert , Reed Darrin K. , Tóth Brigitta , Best Virginia , Majdak Piotr , Colburn H. Steven , Shinn-Cunningham Barbara 
Published: August 2017

Significance
Previous studies demonstrated “auditory looming bias” exclusively by manipulating overall sound intensity. Hence, it is not clear whether this bias truly reflects perceptual differences in sensitivity to motion direction rather than changes in intensity. We manipulated individualized spectral cues to create stimuli that were perceived as either approaching or receding, while controlling loudness. We assessed discrimination of motion direction and analyzed simultaneously recorded neural responses using electroencephalography. Our results show both behavioral and neural evidence of looming bias. Therefore, our study demonstrates that the bias is truly about perceived motion in distance, not intensity changes.