bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acoustic coordinated reset therapy for tinnitus with perceptually relevant frequency spacing and levels
Authors: Tass Peter A. , Silchenko Alexander N. , Popelka Gerald R. 
Published: September 2019

AbstractAcoustic coordinated reset (CR) therapy based on neuromodulation and neuroplasticity principles has been proposed for the treatment of tonal tinnitus. The original therapy involved periodic delivery of randomly ordered sequences of four low-level tones centered around the frequency of a tone that matched the tinnitus pitch, fT, with fixed ratios relative to fT and delivered several hours/day over several weeks. Here we transform the original CR tone selection method to a more perceptually-relevant equivalent rectangular bandwidth (ERB) frequency scale, the ERBN-number scale. Specifically, we provide a mathematical model that enables calculation of CR tones that accounts for fT- and hearing loss-related ERB widening and ERB overlaps and gaps of CR tone alignments. Further, the model ensures symmetric CR tone alignments based on modelling studies that indicate the effect is optimal if the CR stimuli are symmetrically spaced relative to the tinnitus-related population of abnormally synchronized cortical neurons to activate the adjacent sub-populations. We also present experimentally testable ERB-based CR tone alignment strategies and explain how to use the ERB-based model in experiments, clinical studies, other types of tinnitus sound treatment such as tailor-made notch music training and limitations of our approach.
Haploinsufficiency of Transferrin Receptor 1 Impairs Angiogenesis with Reduced Mitochondrial Complex I in Mice with Limb Ischemia
Authors: Okuno Keisuke , Naito Yoshiro , Yasumura Seiki , Sawada Hisashi , Asakura Masanori , Masuyama Tohru , Ishihara Masaharu 
Published: September 2019

AbstractLimb ischemia (LI) is a major consequence of peripheral artery disease (PAD) with a high mortality rate. Iron is an essential mineral to maintain physiological function of multiple organs. Intracellular iron transport is regulated by transferrin receptor 1 (TfR1). Although increase in serum ferritin levels has been reported in PAD patients, the mechanism of iron metabolism in LI is still unclear. The aim of this study is to investigate whether TfR1 deletion attenuates LI formation. To generate LI, the left femoral artery of 8–10 week-old C57BL6/J male mice was ligated. Adductor muscles were harvested at 28 days after surgery to investigate iron metabolism. The level of ferritin, intracellular iron storage protein, was higher in ischemic adductor muscles compared to non-ischemic adductor muscles. Level of intracellular iron transport protein, TfR1, was decreased in ischemic adductor muscles. LI was then generated in TfR1 heterozygous deleted mice (TfR1+/−) to examine whether TfR1 contributes to the pathophysiology of LI. Laser Doppler blood flowmetry revealed that blood flow recovery was attenuated in TfR1+/− mice compared to wild type (WT) littermates, along with decreased expression of ferritin and CD31 in ischemic adductor muscles. Since iron is used for energy production in mitochondria, we then assessed mitochondrial complexes in the ischemic adductor muscle. Of interest, expression of mitochondrial complex I, but not complexes II, III, and V in ischemic adductor muscles was significantly reduced in TfR1+/− mice compared to WT mice. Haploinsufficiency of TfR1 attenuated angiogenesis via reduction of mitochondrial complex I in LI in mice.
Early animal evolution and highly oxygenated seafloor niches hosted by microbial mats
Authors: Ding Weiming , Dong Lin , Sun Yuanlin , Ma Haoran , Xu Yihe , Yang Runyu , Peng Yongbo , Zhou Chuanming , Shen Bing 
Published: September 2019

AbstractThe earliest unambiguous evidence for animals is represented by various trace fossils in the latest Ediacaran Period (550–541 Ma), suggesting that the earliest animals lived on or even penetrated into the seafloor. Yet, the O2 fugacity at the sediment-water interface (SWI) for the earliest animal proliferation is poorly defined. The preferential colonization of seafloor as a first step in animal evolution is also unusual. In order to understand the environmental background, we employed a new proxy, carbonate associated ferrous iron (Fecarb), to quantify the seafloor oxygenation. Fecarb of the latest Ediacaran Shibantan limestone in South China, which yields abundant animal traces, ranges from 2.27 to 85.43 ppm, corresponding to the seafloor O2 fugacity of 162 μmol/L to 297 μmol/L. These values are significantly higher than the oxygen saturation in seawater at the contemporary atmospheric pO2 levels. The highly oxygenated seafloor might be attributed to O2 production of the microbial mats. Despite the moderate atmospheric pO2 level, microbial mats possibly provided highly oxygenated niches for the evolution of benthic metazoans. Our model suggests that the O2 barrier could be locally overcome in the mat ground, questioning the long-held belief that atmospheric oxygenation was the key control of animal evolution.
The association between plasma proneurotensin and glucose regulation is modified by country of birth
Authors: Fawad A. , Nilsson P. M. , Struck J. , Bergmann A. , Melander O. , Bennet L. 
Published: September 2019

AbstractThe prevalence of type 2 diabetes (T2D) has increased dramatically in Middle Eastern populations that represent the largest non-European immigrant group in Sweden today. As proneurotensin predicts T2D, the aim of this study was to investigate differences in proneurotensin levels across populations of Middle Eastern and Caucasian origin and to study its associations with indices of glucose regulation. Participants in the age 30 to 75 years, living in Malmö, Sweden, and born in Iraq or Sweden, were recruited from the census register. Anthropometrics and fasting samples were collected and oral glucose tolerance tests conducted assessing insulin secretion (DIo) as well as insulin sensitivity (ISI). A total of 2155 individuals participated in the study, 1398 were Iraqi-born and 757 were Swedish-born participants. Higher fasting proneurotensin levels were observed in Iraqi- compared to Swedish-born participants (137.5 vs. 119.8 pmol/L; p < 0.001) data adjusted for age, sex and body mass index. In Iraqi participants only, plasma proneurotensin was associated with impaired glucose regulation assessed as ISI, DIo and HbA1c, and significant interactions between country of birth and proneurotensin were observed (Pinteraction ISI = 0.048; Pinteraction DIo = 0.014; PinteractionHbA1c = 0.029). We report higher levels of proneurotensin in the general Middle Eastern population. The finding that Middle Eastern origin modifies the relationship of proneurotensin with indices of glucose regulation suggests that proneurotensin may be a stronger determinant of T2D in Middle Eastern as compared to Caucasian populations. These findings may explain part of the excess T2D risk in the Middle Eastern population but needs to be explored further.
Cell-free nuclear, but not mitochondrial, DNA concentrations correlate with the early host inflammatory response after severe trauma
Authors: Stortz Julie A. , Hawkins Russell B. , Holden David C. , Raymond Steven L. , Wang Zhongkai , Brakenridge Scott C. , Cuschieri Joseph , Moore Frederick A. , Maier Ronald V. , Moldawer Lyle L. , Efron Philip A. 
Published: September 2019

AbstractSevere blunt trauma is associated with an early ‘genomic storm’ which causes simultaneous up- and down-regulation of host protective immunity. Excessive inflammation can lead to organ injury. In the absence of infection, the inflammatory response is presumably driven by release of endogenous alarmins called danger-associated molecular patterns (DAMPs), which initiate immune responses through pattern-recognition receptors (PRR). Here we examined the relationship between concentrations of cell-free (cf) nuclear DNA (ncDNA) and mitochondrial DNA (mtDNA) within 24 hours post trauma with circulating leukocyte transcriptomics and plasma IL-6 concentrations, as well as the patients’ clinical trajectories. In 104 patients enrolled from two level-1 trauma centers, ncDNA and mtDNA concentrations were increased within 24 hours of severe trauma, but only ncDNA concentrations correlated with leukocyte gene expression and outcomes. Surprisingly, ncDNA, not mtDNA concentrations, were significantly elevated in trauma patients who developed chronic critical illness versus rapid clinical recovery. Plasma IL-6 and leukocyte transcriptomics were better predictors of outcomes than cfDNA levels. Although mtDNA and ncDNA are significantly increased in the immediate post-trauma period, the dramatic inflammatory and gene expression changes seen after severe trauma are only weakly correlated with ncDNA concentrations, and more importantly, mtDNA concentrations are not associated with adverse clinical trajectories.
Disrupted brain structural connectivity in Pediatric Bipolar Disorder with psychosis
Authors: Fernandes Henrique M. , Cabral Joana , van Hartevelt Tim J. , Lord Louis-David , Gleesborg Carsten , Møller Arne , Deco Gustavo , Whybrow Peter C. , Petrovic Predrag , James Anthony C. , Kringelbach Morten L. 
Published: September 2019

AbstractBipolar disorder (BD) has been linked to disrupted structural and functional connectivity between prefrontal networks and limbic brain regions. Studies of patients with pediatric bipolar disorder (PBD) can help elucidate the developmental origins of altered structural connectivity underlying BD and provide novel insights into the aetiology of BD. Here we compare the network properties of whole-brain structural connectomes of euthymic PBD patients with psychosis, a variant of PBD, and matched healthy controls. Our results show widespread changes in the structural connectivity of PBD patients with psychosis in both cortical and subcortical networks, notably affecting the orbitofrontal cortex, frontal gyrus, amygdala, hippocampus and basal ganglia. Graph theoretical analysis revealed that PBD connectomes have fewer hubs, weaker rich club organization, different modular fingerprint and inter-modular communication, compared to healthy participants. The relationship between network features and neurocognitive and psychotic scores was also assessed, revealing trends of association between patients’ IQ and affective psychotic symptoms with the local efficiency of the orbitofrontal cortex. Our findings reveal that PBD with psychosis is associated with significant widespread changes in structural network topology, thus strengthening the hypothesis of a reduced capacity for integrative processing of information across brain regions. Localised network changes involve core regions for emotional processing and regulation, as well as memory and executive function, some of which show trends of association with neurocognitive faculties and symptoms. Together, our findings provide the first comprehensive characterisation of the alterations in local and global structural brain connectivity and network topology, which may contribute to the deficits in cognition and emotion processing and regulation found in PBD.
Globally elevating the AGE clearance receptor, OST48, does not protect against the development of diabetic kidney disease, despite improving insulin secretion
Authors: Zhuang Aowen , Yap Felicia Y. T. , McCarthy Domenica , Leung Chris , Sourris Karly C. , Penfold Sally A. , Thallas-Bonke Vicki , Coughlan Melinda T. , Schulz Benjamin L. , Forbes Josephine M. 
Published: September 2019

AbstractThe accumulation of advanced glycation end products (AGEs) have been implicated in the development and progression of diabetic kidney disease (DKD). There has been interest in investigating the potential of AGE clearance receptors, such as oligosaccharyltransferase-48 kDa subunit (OST48) to prevent the detrimental effects of excess AGE accumulation seen in the diabetic kidney. Here the objective of the study was to increase the expression of OST48 to examine if this slowed the development of DKD by facilitating the clearance of AGEs. Groups of 8-week-old heterozygous knock-in male mice (n = 9–12/group) over-expressing the gene encoding for OST48, dolichyl-diphosphooligosaccharide-protein glycosyltransferase (DDOST+/−) and litter mate controls were randomised to either (i) no diabetes or (ii) diabetes induced via multiple low-dose streptozotocin and followed for 24 weeks. By the study end, global over expression of OST48 increased glomerular OST48. This facilitated greater renal excretion of AGEs but did not affect circulating or renal AGE concentrations. Diabetes resulted in kidney damage including lower glomerular filtration rate, albuminuria, glomerulosclerosis and tubulointerstitial fibrosis. In diabetic mice, tubulointerstitial fibrosis was further exacerbated by global increases in OST48. There was significantly insulin effectiveness, increased acute insulin secretion, fasting insulin concentrations and AUCinsulin observed during glucose tolerance testing in diabetic mice with global elevations in OST48 when compared to diabetic wild-type littermates. Overall, this study suggested that despite facilitating urinary-renal AGE clearance, there were no benefits observed on kidney functional and structural parameters in diabetes afforded by globally increasing OST48 expression. However, the improvements in insulin secretion seen in diabetic mice with global over-expression of OST48 and their dissociation from effects on kidney function warrant future investigation.
Quantitative comparative analysis of human erythrocyte surface proteins between individuals from two genetically distinct populations
Authors: Ravenhill Benjamin J. , Kanjee Usheer , Ahouidi Ambroise , Nobre Luis , Williamson James , Goldberg Jonathan M. , Antrobus Robin , Dieye Tandakha , Duraisingh Manoj T. , Weekes Michael P. 
Published: September 2019

AbstractRed blood cells (RBCs) play a critical role in oxygen transport, and are the focus of important diseases including malaria and the haemoglobinopathies. Proteins at the RBC surface can determine susceptibility to disease, however previous studies classifying the RBC proteome have not used specific strategies directed at enriching cell surface proteins. Furthermore, there has been no systematic analysis of variation in abundance of RBC surface proteins between genetically disparate human populations. These questions are important to inform not only basic RBC biology but additionally to identify novel candidate receptors for malarial parasites. Here, we use ‘plasma membrane profiling’ and tandem mass tag-based mass spectrometry to enrich and quantify primary RBC cell surface proteins from two sets of nine donors from the UK or Senegal. We define a RBC surface proteome and identify potentialPlasmodiumreceptors based on either diminished protein abundance, or increased variation in RBCs from West African individuals.
Ex vivo toxicological evaluation of experimental anticancer gold(i) complexes with lansoprazole-type ligands
Authors: Estrada-Ortiz Natalia , Lopez-Gonzales Elena , Woods Ben , Stürup Stefan , de Graaf Inge A. M. , Groothuis Geny M. M. , Casini Angela 
Published: September 2019

AbstractGold-based compounds are of great interest in the field of medicinal chemistry as novel therapeutic (anticancer) agents due to their peculiar reactivity and mechanisms of action with respect to organic drugs. Despite their promising pharmacological properties, the possible toxic effects of gold compounds need to be carefully evaluated in order to optimize their design and applicability. This study reports on the potential toxicity of three experimental gold-based anticancer compounds featuring lansoprazole ligands (1–3) studied in an ex vivo model, using rat precision cut kidney and liver slices (PCKS and PCLS, respectively). The results showed a different toxicity profile for the tested compounds, with the neutral complex 2 being the least toxic, even less toxic than cisplatin, followed by the cationic complex 1. The dinuclear cationic gold complex 3 was the most toxic in both liver and kidney slices. This result correlated with the metal uptake of the different compounds assessed by ICP-MS, where complex 3 showed the highest accumulation of gold in liver and kidney slices. Interestingly compound 1 showed the highest selectivity towards cancer cells compared to the healthy tissues. Histomorphology evaluation showed a similar pattern for all three Au(i) complexes, where the distal tubular cells suffered the most extensive damage, in contrast to the damage in the proximal tubules induced by cisplatin. The binding of representative gold compounds with the model ubiquitin was also studied by ESI-MS, showing that after 24 h incubation only ‘naked’ Au ions were bound to the protein following ligands’ loss. The mRNA expression of stress response genes appeared to be similar for both evaluated organs, suggesting oxidative stress as the possible mechanism of toxicity. The obtained results open new perspectives towards the design and testing of bifunctional gold complexes with chemotherapeutic applications.
Signatures of diffuse interstellar gas in the Galaxy Evolution Explorer all-sky survey
Authors: Armengot Marcelo , Gómez de Castro Ana I. 
Published: September 2019

Context. The all-sky survey run by the Galaxy Evolution Explorer (GALEX AIS) mapped about 85% of the Galaxy at ultraviolet (UV) wavelengths and detected the diffuse UV background produced by the scattering of the radiation from OBA stars by interstellar dust grains. Against this background, diffuse weak structures were detected as well as the UV counterparts to nebulae and molecular clouds.
Aims. To make full profit of the survey, unsupervised and semi-supervised procedures need to be implemented. The main objective of this work is to implement and analyze the results of the method developed by us for the blind detection of ISM features in the GALEX AIS.
Methods. Most ISM features are detected at very low signal levels (dark filaments, globules) against the already faint UV background. We have defined an index, the UV background fluctuations index (or UBF index), to identify areas of the sky where these fluctuations are detected. The algorithm is applied to the images obtained in the far-UV (1344–1786 Å) band since this is less polluted by stellar sources, facilitating the automated detection.
Results. The UBF index is shown to be sensitive to the main star forming regions within the Gould’s Belt, and to some prominent loops like Loop I or the Eridanus and Monogem areas. The catalog with the UBF index values is made available online to the community.
Discovery of a 21 Myr old stellar population in the Orion complex
Authors: Kos Janez , Bland-Hawthorn Joss , Asplund Martin , Buder Sven , Lewis Geraint F. , Lin Jane , Martell Sarah L. , Ness Melissa K. , Sharma Sanjib , De Silva Gayandhi M. , Simpson Jeffrey D. , Zucker Daniel B. , Zwitter Tomaž , Čotar Klemen , Spina Lorenzo 
Published: September 2019

Context. The Orion complex is arguably the most studied star-forming region in the Galaxy. While stars are still being born in the Orion nebula, the oldest part was believed to be no more than 13 Myr old.
Aims. In order to study the full hierarchy of star formation across the Orion complex, we perform a clustering analysis of the Ori OB1a region using new stellar surveys and derive robust ages for each identified stellar aggregate.
Methods. We use Gaia DR2 parameters supplemented with radial velocities from the GALAH and APOGEE surveys to perform clustering of the Ori OB1a association. Five overdensities are resolved in a six-dimensional parameter space (positions, distance, proper motions, and radial velocity). Most correspond to previously known structures (ASCC 16, 25 Orionis, ASCC 20, ASCC 21). We use Gaia DR2, Pan-STARRS1 and 2MASS photometry to fit isochrones to the colour-magnitude diagrams of the identified clusters. The ages of the clusters can thus be measured with ∼10% precision.
Results. While four of the clusters have ages between 11 and 13 Myr, the ASCC 20 cluster stands out at an age of 21 ± 3 Myr. This is significantly greater than the age of any previously known component of the Orion complex. To some degree, all clusters overlap in at least one of the six phase-space dimensions.
Conclusions. We argue that the formation history of the Orion complex, and its relation to the Gould belt, must be reconsidered. A significant challenge in reconstructing the history of the Ori OB1a association is to understand the impact of the newly discovered 21 Myr old population on the younger parts of the complex, including their formation.
Zum Umgang mit Widerstand in einer kontinuierlich arbeitenden Balintgruppe als „emotionaler Spielwiese“ – kritische Reflexionen nach über zwei Jahrzehnten
Authors: Zimmermann Wolfram 
Published: September 2019

ZusammenfassungGegenstand der vorliegenden Arbeit sind kritisch reflektierte Veränderungen des emotionalen Klimas in den letzten Jahren in der Leitung einer sehr kontinuierlich arbeitenden Balintgruppe in Bernau. Sie wird vom Autor seit mehr als 22 Jahren als anerkannter und zertifizierter Qualitätszirkel geleitet. Bis Ende 2017 wurde diese Balintgruppe in der eigenen Psychotherapie-Praxis des Autors durchgeführt. Nach der Beendigung dieser eigenen Praxistätigkeit wurde der Autor von der KV Brandenburg mit einer sehr persönlichen Anerkennung der bisherigen Leistungen gebeten, diese Balintgruppe in anderen Räumlichkeiten auch weiterhin zu führen. Dies konnte mit erfolgreichem Engagement in einer Internistischen Gemeinschaftspraxis seit Anfang 2018 realisiert werden. Der Autor stellte aber dabei in den letzten Jahren relevante Veränderungen im emotionalen Klima in dieser Gruppe fest. Diese immer sehr engagiert arbeitende Balintgruppe wurde von einer älteren Kollegin früher immer gern als sogenannte „emotionale Spielwiese“ erlebt . Hier wurde v. a. sehr viel innerer affektiver Erlebnisraum eröffnet, wurde unmittelbare Kommunikation von Gefühlen, von mannigfaltigen inneren Bildern und lebhaften Körperempfindungen realisiert. Genau aber dieser erlebte intensive emotionale Charakter hat sich in der letzten Zeit verändert, die „emotionale Spielwiese“ wird irgendwie weniger gestaltet. Dies wird am Beispiel von häufigeren rationalisierenden und diagnostischen Erklärungen bzw. Ratschlägen besonders einzelner Teilnehmerinnen und einer entsprechenden Fallvignette verdeutlicht. Zugleich werden Bemühungen des Leiters dieser Bernauer Balintgruppe aufgezeigt, diese „emotionale Spielwiese“ wieder verstärkt zu nutzen. Direkt angeregt wurde diese vorliegende Arbeit durch hoch interessante Überlegungen zum Umgang mit eventuell vergleichbaren „kritischen Ereignissen“ in einfachen psychsomatischen Gruppen vor Ort mit weniger vorgebildeten TeilnehmerInnen und einem dabei methodisch- vorgenommenen Vergleich von „Alten und Neuem“ [vgl. 6, 16ff.] sowie einer kritischen Analyse der Balintgruppenleitung anlässlich der Silser Studienwoche 2017 in der Schweiz [vgl. 7]