bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable number of TMC1-dependent mechanotransducer channels underlie tonotopic conductance gradients in the cochlea
Authors: Beurg Maryline , Cui Runjia , Goldring Adam C. , Ebrahim Seham , Fettiplace Robert , Kachar Bechara 
Published: May 2018

AbstractFunctional mechanoelectrical transduction (MET) channels of cochlear hair cells require the presence of transmembrane channel-like protein isoforms TMC1 or TMC2. We show that TMCs are required for normal stereociliary bundle development and distinctively influence channel properties. TMC1-dependent channels have larger single-channel conductance and in outer hair cells (OHCs) support a tonotopic apex-to-base conductance gradient. Each MET channel complex exhibits multiple conductance states in ~50 pS increments, basal MET channels having more large-conductance levels. Using mice expressing fluorescently tagged TMCs, we show a three-fold increase in number of TMC1 molecules per stereocilium tip from cochlear apex to base, mirroring the channel conductance gradient in OHCs. Single-molecule photobleaching indicates the number of TMC1 molecules per MET complex changes from ~8 at the apex to ~20 at base. The results suggest there are varying numbers of channels per MET complex, each requiring multiple TMC1 molecules, and together operating in a coordinated or cooperative manner.
Mapping higher-order relations between brain structure and function with embedded vector representations of connectomes
Authors: Rosenthal Gideon , Váša František , Griffa Alessandra , Hagmann Patric , Amico Enrico , Goñi Joaquín , Avidan Galia , Sporns Olaf 
Published: May 2018

AbstractConnectomics generates comprehensive maps of brain networks, represented as nodes and their pairwise connections. The functional roles of nodes are defined by their direct and indirect connectivity with the rest of the network. However, the network context is not directly accessible at the level of individual nodes. Similar problems in language processing have been addressed with algorithms such as word2vec that create embeddings of words and their relations in a meaningful low-dimensional vector space. Here we apply this approach to create embedded vector representations of brain networks or connectome embeddings (CE). CE can characterize correspondence relations among brain regions, and can be used to infer links that are lacking from the original structural diffusion imaging, e.g., inter-hemispheric homotopic connections. Moreover, we construct predictive deep models of functional and structural connectivity, and simulate network-wide lesion effects using the face processing system as our application domain. We suggest that CE offers a novel approach to revealing relations between connectome structure and function.
Gut vagal sensory signaling regulates hippocampus function through multi-order pathways
Authors: Suarez Andrea N. , Hsu Ted M. , Liu Clarissa M. , Noble Emily E. , Cortella Alyssa M. , Nakamoto Emily M. , Hahn Joel D. , de Lartigue Guillaume , Kanoski Scott E. 
Published: May 2018

AbstractThe vagus nerve is the primary means of neural communication between the gastrointestinal (GI) tract and the brain. Vagally mediated GI signals activate the hippocampus (HPC), a brain region classically linked with memory function. However, the endogenous relevance of GI-derived vagal HPC communication is unknown. Here we utilize a saporin (SAP)-based lesioning procedure to reveal that selective GI vagal sensory/afferent ablation in rats impairs HPC-dependent episodic and spatial memory, effects associated with reduced HPC neurotrophic and neurogenesis markers. To determine the neural pathways connecting the gut to the HPC, we utilize monosynaptic and multisynaptic virus-based tracing methods to identify the medial septum as a relay connecting the medial nucleus tractus solitarius (where GI vagal afferents synapse) to dorsal HPC glutamatergic neurons. We conclude that endogenous GI-derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem–septal pathway, thereby identifying a previously unknown role for the gut–brain axis in memory control.
Valley dependent anisotropic spin splitting in silicon quantum dots
Authors: Ferdous Rifat , Kawakami Erika , Scarlino Pasquale , Nowak Michał P. , Ward D. R. , Savage D. E. , Lagally M. G. , Coppersmith S. N. , Friesen Mark , Eriksson Mark A. , Vandersypen Lieven M. K. , Rahman Rajib 
Published: May 2018

AbstractSpin qubits hosted in silicon (Si) quantum dots (QD) are attractive due to their exceptionally long coherence times and compatibility with the silicon transistor platform. To achieve electrical control of spins for qubit scalability, recent experiments have utilized gradient magnetic fields from integrated micro-magnets to produce an extrinsic coupling between spin and charge, thereby electrically driving electron spin resonance (ESR). However, spins in silicon QDs experience a complex interplay between spin, charge, and valley degrees of freedom, influenced by the atomic scale details of the confining interface. Here, we report experimental observation of a valley dependent anisotropic spin splitting in a Si QD with an integrated micro-magnet and an external magnetic field. We show by atomistic calculations that the spin-orbit interaction (SOI), which is often ignored in bulk silicon, plays a major role in the measured anisotropy. Moreover, inhomogeneities such as interface steps strongly affect the spin splittings and their valley dependence. This atomic-scale understanding of the intrinsic and extrinsic factors controlling the valley dependent spin properties is a key requirement for successful manipulation of quantum information in Si QDs.
Temperature dependence of the superconducting energy gaps in Ca9.35La0.65(Pt3As8)(Fe2As2)5 single crystal
Authors: Seo Yu-il , Choi Woo-jae , Ahmad D. , Kimura Shin-ichi , Kwon Yong Seung 
Published: May 2018

AbstractWe measured the optical reflectivity R(ω) for an underdoped (Ca0.935La0.065)10(Pt3As8)(Fe2As2)5 single crystal and obtained the optical conductivity $${\sigma }_{1}(\omega )$$

σ

1

(
ω
)

using the K-K transformation. The normal state $${\sigma }_{1}(\omega )$$

σ

1

(
ω
)

at 30 K is well fitted by a Drude-Lorentz model with two Drude components (ωp1 = 1446 cm−1 and ωp2 = 6322 cm−1) and seven Lorentz components. Relative reflectometry was used to accurately determine the temperature dependence of the superconducting gap at various temperatures below Tc. The results clearly show the opening of a superconducting gap with a weaker second gap structure; the magnitudes for the gaps are estimated from the generalized Mattis-Bardeen model to be Δ1 = 30 and Δ2 = 50 cm−1, respectively, at T = 8 K, which both decrease with increasing temperature. The temperature dependence of the gaps was not consistent with one-band BCS theory but was well described by a two-band (hence, two gap) BCS model with interband interactions. The temperature dependence of the superfluid density is flat at low temperatures, indicating an s-wave full-gap superconducting state.
Attraction of posture and motion-trajectory elements of conspecific biological motion in medaka fish
Authors: Shibai Atsushi , Arimoto Tsunehiro , Yoshinaga Tsukasa , Tsuchizawa Yuta , Khureltulga Dashdavaa , Brown Zuben P. , Kakizuka Taishi , Hosoda Kazufumi 
Published: May 2018

AbstractVisual recognition of conspecifics is necessary for a wide range of social behaviours in many animals. Medaka (Japanese rice fish), a commonly used model organism, are known to be attracted by the biological motion of conspecifics. However, biological motion is a composite of both body-shape motion and entire-field motion trajectory (i.e., posture or motion-trajectory elements, respectively), and it has not been revealed which element mediates the attractiveness. Here, we show that either posture or motion-trajectory elements alone can attract medaka. We decomposed biological motion of the medaka into the two elements and synthesized visual stimuli that contain both, either, or none of the two elements. We found that medaka were attracted by visual stimuli that contain at least one of the two elements. In the context of other known static visual information regarding the medaka, the potential multiplicity of information regarding conspecific recognition has further accumulated. Our strategy of decomposing biological motion into these partial elements is applicable to other animals, and further studies using this technique will enhance the basic understanding of visual recognition of conspecifics.
Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies
Authors: Akbaraly Tasnime , Würtz Peter , Singh-Manoux Archana , Shipley Martin J. , Haapakoski Rita , Lehto Maili , Desrumaux Catherine , Kähönen Mika , Lehtimäki Terho , Mikkilä Vera , Hingorani Aroon , Humphries Steve E. , Kangas Antti J. , Soininen Pasi , Raitakari Olli , Ala-Korpela Mika , Kivimäki Mika 
Published: May 2018

AbstractDiet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations - the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 ± 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 ± 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.
Pomegranate action in curbing the incidence of liver injury triggered by Diethylnitrosamine by declining oxidative stress via Nrf2 and NFκB regulation
Authors: Husain Hadiya , Latief Uzma , Ahmad Riaz 
Published: May 2018

AbstractUnearthing and employment of healthy substitutes is now in demand to tackle a number of diseases due to the excessive repercussions of synthetic drugs. In this frame of reference pomegranate juice (PGJ) is a boon comprising of anthocyanins and hydrolysable tannins, known for its anti-oxidant and anti-inflammatory properties. Despite various documented roles of PGJ, there are no studies on antifibrotic potential in NDEA-induced mammalian liver fibrotic model. Hepatic fibrosis in rats was induced by the intra-peritoneal injection of NDEA (10 mlkg−1b.wt. of 1% NDEA) in two weeks. Biochemical, histopathological and ultra-structural studies were carried out on control, fibrotic and treated rats. The liver function indices and LPO were increased significantly by intoxication of NDEA. The antioxidant status was disturbed with the decrease in SOD, GST and catalase in the liver and membrane-ATPases as well. Histopathological observations by H&E, M&T, picro-sirius and ultra-structural scrutiny by SEM and TEM indicated liver damage and increase in COX2 and α-SMA by NDEA which was successfully rectified by the supplementation of PGJ. PGJ abrogates liver fibrosis instigated by NDEA in Wistar rats by declining oxidative stressviaregulation of Nrf2 and NFκB. These findings point towards pomegranate as a potential and efficacious therapeutic agent against liver fibrosis.
Hit-Gel: Streamlining in-gel protein digestion for high-throughput proteomics experiments
Authors: Swart Corné , Martínez-Jaime Silvia , Gorka Michal , Zander Kerstin , Graf Alexander 
Published: May 2018

AbstractIn-gel digestion has been used as a standard method for the preparation of protein samples for mass spectrometry analysis for over 25 years. Traditional in gel-digestion procedures require extensive sample handling, are prone to contamination and not compatible with high-throughput sample preparation. To address these shortcomings, we have modified the conventional in-gel digestion procedure for high-throughput proteomics studies. The modified method, termed “High Throughput in Gel digestion” (HiT-Gel), is based on a 96-well plate format which results in a drastic reduction in labour intensity and sample handling. Direct comparison revealed that HiT-Gel reduces technical variation and significantly decreases sample contamination over the conventional in-gel digestion method. HiT-Gel also produced superior results when a single protein band was excised from a gel and processed by in-gel digestion. Moreover, we applied Hit-Gel for a mass spectrometry analysis of Arabidopsis thaliana protein complexes separated by native PAGE in 24 fractions and four biological replicates. We show that the high throughput capacity of HiT-Gel facilitates large scale studies with high sample replication or detailed fractionation. Our method can easily be implemented as it does not require specialised laboratory equipment.
Linking organismal growth, coping styles, stress reactivity, and metabolism via responses against a selective serotonin reuptake inhibitor in an insect
Authors: Krams Indrikis , Trakimas Giedrius , Kecko Sanita , Elferts Didzis , Krams Ronalds , Luoto Severi , Rantala Markus J. , Mänd Marika , Kuusik Aare , Kekäläinen Jukka , Jõers Priit , Kortet Raine , Krama Tatjana 
Published: May 2018

AbstractEvidence suggests that brain serotonin (5-HT) is one of the central mediators of different types of animal personality. We tested this assumption in field crickets Gryllus integer using a selective serotonin reuptake inhibitor (SSRI). Crickets were selected for slow and rapid development and tested for their coping styles under non-stressful conditions (time spent exploring a novel object). Resting metabolic rate, maximum metabolic rate and latency to resume activity were measured under stressful conditions (stress reactivity). Measurements were taken (i) before and (ii) during the SSRI treatment. Before the SSRI treatment, a strong negative correlation was observed between coping style and stress reactivity, which suggests the existence of a behavioral syndrome. After the SSRI treatment, the syndrome was no longer evident. The results of this study show that 5-HT may be involved in regulating behavior not only along a stress reactivity gradient but also along a coping styles axis. The relationship between personality and the strength and direction of 5-HT treatment on observed behaviors indicates trait-like individual differences in 5-HT signaling. Overall, these findings do not support recent ideas arising from the pace-of-life syndrome (POLS) hypothesis, which predict higher exploration and metabolic rates in rapidly developing bold animals.
Multidrug resistant pathogens respond differently to the presence of co-pathogen, commensal, probiotic and host cells
Authors: Chan Agnes P. , Choi Yongwook , Brinkac Lauren M. , Krishnakumar Radha , DePew Jessica , Kim Maria , Hinkle Mary K. , Lesho Emil P. , Fouts Derrick E. 
Published: May 2018

AbstractIn light of the ongoing antimicrobial resistance crisis, there is a need to understand the role of co-pathogens, commensals, and the local microbiome in modulating virulence and antibiotic resistance. To identify possible interactions that influence the expression of virulence or survival mechanisms in both the multidrug-resistant organisms (MDROs) and human host cells, unique cohorts of clinical isolates were selected for whole genome sequencing with enhanced assembly and full annotation, pairwise co-culturing, and transcriptome profiling. The MDROs were co-cultured in pairwise combinations either with: (1) another MDRO, (2) skin commensals (Staphylococcus epidermidis and Corynebacterium jeikeium), (3) the common probiotic Lactobacillus reuteri, and (4) human fibroblasts. RNA-Seq analysis showed distinct regulation of virulence and antimicrobial resistance gene responses across different combinations of MDROs, commensals, and human cells. Co-culture assays demonstrated that microbial interactions can modulate gene responses of both the target and pathogen/commensal species, and that the responses are specific to the identity of the pathogen/commensal species. In summary, bacteria have mechanisms to distinguish between friends, foe and host cells. These results provide foundational data and insight into the possibility of manipulating the local microbiome when treating complicated polymicrobial wound, intra-abdominal, or respiratory infections.
Protection of Thiol Groups on the Surface of Magnetic Adsorbents and Their Application for Wastewater Treatment
Authors: Melnyk Inna V. , Pogorilyi Roman P. , Zub Yuriy L. , Vaclavikova Miroslava , Gdula Karolina , Dąbrowski Andrzej , Seisenbaeva Gulaim A. , Kessler Vadim G. 
Published: May 2018

AbstractThe magnetite nanoparticles were functionalized with silica shells bearing mercaptopropyl (monofunctional) and mercaptopropyl-and-alkyl groups (bifunctional) by single-step sol-gel technique. The influence of synthetic conditions leading to increased amounts of active functional groups on the surface and improved capacity in the uptake of Ag(I), Cd(II), Hg(II), and Pb(II) cations was revealed. The physicochemical properties of obtained magnetic nanocomposites were investigated by FTIR, Raman, XRD, TEM, SEM, low-temperature nitrogen ad-/desorption measurements, TGA, and chemical microanalysis highlighting the efficiency of functionalization and mechanisms of the preparation procedures. The removal of the main group of heavy metal cations was studied in dependence from the pH, contact time and equilibrium concentration to analyze the complexes composition for the large scale production of improved adsorbents. It was demonstrated that introduction of the alkyl groups into the surface layer prevents the formation of the disulfide bonds between adjacent thiol groups. The obtained adsorbents were employed to treat real wastewater from Ruskov, Slovakia with concentration of Fe 319 ng/cm3, Cu 23.7 ng/cm3, Zn 36 ng/cm3, Mn 503 ng/cm3, Al 21 ng/cm3, As 34 ng/cm3, Pb 5.8 ng/cm3, Ni 35 ng/cm3, Co 4.2 ng/cm3, Cr 9.4 ng/cm3, Sb 6 ng/cm3, Cd 5 ng/cm3. These materials proved to be highly effective in the removal of 50% of all metal ions, espeсially Zn, Cd, and Pb ions from it and turned recyclable, opening for their sustainable use in water purification.
MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice
Authors: Perera Agampodi Promoda , Fernando Ruchira , Shinde Tanvi , Gundamaraju Rohit , Southam Benjamin , Sohal Sukhwinder Singh , Robertson Avril A. B. , Schroder Kate , Kunde Dale , Eri Rajaraman 
Published: May 2018

AbstractMCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1β, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1β release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.
Comprehensive analysis of CTNNB1 in adrenocortical carcinomas: Identification of novel mutations and correlation to survival
Authors: Maharjan Rajani , Backman Samuel , Åkerström Tobias , Hellman Per , Björklund Peyman 
Published: May 2018

AbstractThe Wnt/β-Catenin signaling pathway is one of the most frequently altered pathways in adrenocortical carcinomas (ACCs). The aim of this study was to investigate the status of Wnt/β-Catenin signaling pathway by analyzing the expression level of β-Catenin and the mutational status of APC, AXIN2, CTNNB1, and ZNRF3 in ACCs. Mutations in APC, CTNNB1, ZNRF3 and homozygous deletions in ZNRF3 were observed in 3.8% (2/52), 11.5% (6/52), 1.9% (1/52) and 17.3% (9/52) of the cohort respectively. Novel interstitial deletions in CTNNB1 spanning intron 1 to exon 3/intron 3 were also found in 7.7% (4/52) of the tumours. All the observed alterations were mutually exclusive. Nuclear accumulation of β-Catenin, increased expression of Cyclin D1 and significantly higher expression of AXIN2 (p = 0.0039), ZNRF3 (p = 0.0032) and LEF1(p = 0.0090) observed in the tumours harbouring the deletion in comparison to tumours without CTNNB1 mutation demonstrates that the truncated β-Catenin is functionally active and erroneously activates the downstream targets. Significantly lower overall survival rate in patients with tumours harbouring alterations in APC/CTNNB1/ZNRF3 in comparison to those without mutation was observed. In conclusion, the discovery of novel large deletions in addition to the point mutations in CTNNB1 infers that activation of Wnt/β-Catenin pathway via alterations in CTNNB1 occurs frequently in ACCs. We also confirm that alterations in Wnt/β-Catenin signaling pathway members have a negative effect on overall survival of patients.
Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice
Authors: Cabral-Costa J. V. , Andreotti D. Z. , Mello N. P. , Scavone C. , Camandola S. , Kawamoto E. M. 
Published: May 2018

AbstractPhosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention – intermittent fasting (IF) – and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test – an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.