bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early‐Warning Signals for Marine Anoxic Events
Authors: Hennekam Rick , van der Bolt Bregje , van Nes Egbert H. , de Lange Gert J. , Scheffer Marten , Reichart Gert‐Jan 
Published: October 2020

AbstractPredicting which marine systems are close to abrupt transitions into oxygen‐deficient conditions (“anoxia”) is notoriously hard but important—as rising temperatures and coastal eutrophication drive many marine systems toward such tipping points. Rapid oxic‐to‐anoxic transitions occurred regularly within the eastern Mediterranean Sea on (multi)centennial time scales, and hence, its sedimentary archive allows exploring statistical methods that can indicate approaching tipping points. The here presented high‐resolution reconstructions of past oxygen dynamics in the Mediterranean Sea reveal that early‐warning signals in these deoxygenation time series occurred long before fast transitions to anoxia. These statistical indicators (i.e., rise in autocorrelation and variance) are hallmarks of so‐called critical slowing down, signaling a steady loss of resilience of the oxygenated state as the system approaches a tipping point. Hence, even without precise knowledge of the mechanisms involved, early‐warning signals for widespread anoxia in marine systems are recognizable using an appropriate statistical approach.
Local‐Time and Vertical Characteristics of Quasi‐6‐Day Oscillation in the Ionosphere During the 2019 Antarctic Sudden Stratospheric Warming
Authors: Lin J. T. , Lin C. H. , Rajesh P. K. , Yue Jia , Lin C. Y. , Matsuo T. 
Published: October 2020

AbstractThis study investigates new characteristics of ionospheric modulations driven by quasi‐6‐day wave (Q6DW) burst following a rare Antarctic sudden stratospheric warming (SSW) in September 2019. Local‐time and vertical variations of the amplitude and phase of quasi‐6‐day oscillation (Q6DO) in the ionosphere are examined by using data assimilation analysis of electron density from three‐dimensional Global Ionosphere Specification (GIS). The maximum amplitudes of Q6DO are located symmetrically ±20° off the magnetic equator at ~12 LT, with a secondary peak at 17 LT. The amplitude of Q6DO weakens at 15 LT, with a sudden phase shift, suggesting multiple dynamo processes driving the Q6DO‐related ionospheric variations. The altitude‐latitude structure of Q6DO shows that the ionospheric modulations extend beyond the equatorial ionization anomaly, indicating the wind dynamo source regions at higher latitudes. A likely physical mechanism is discussed based on possible interactions of Q6DW and semidiurnal migrating tides leading to the dynamo modulation and phase differences.
Identification of two QTLs associated with high fruit acidity in apple using pooled genome sequencing analysis
Authors: Ban Seunghyun , Xu Kenong 
Published: October 2020

AbstractAcidity is a critical component determining apple fruit quality. Previous studies reported two major acidity quantitative trait loci (QTLs) on linkage groups (LGs) 16 (Ma) and 8 (Ma3), respectively, and their homozygous genotypes mama and ma3ma3 usually confer low titratable acidity (TA) (<3.0 mg ml−1) to apple fruit. However, apples of genotypes Ma- (MaMa and Mama) or Ma3- (Ma3Ma3 and Ma3ma3) frequently show an acidity range spanning both regular (TA 3.0–10.0 mg ml−1) and high (TA > 10 mg ml−1) acidity levels. To date, the genetic control for high-acidity apples remains essentially unknown. In order to map QTLs associated with high acidity, two genomic DNA pools, one for high acidity and the other for regular acidity, were created in an interspecific F1 population Royal Gala (Malus domestica) × PI 613988 (M. sieversii) of 191 fruit-bearing progenies. By Illumina paired-end sequencing of the high and regular acidity pools, 1,261,640 single-nucleotide variants (SNVs) commonly present in both pools were detected. Using allele frequency directional difference and density (AFDDD) mapping approach, one region on chromosome 4 and another on chromosome 6 were identified to be putatively associated with high acidity, and were named Ma6 and Ma4, respectively. Trait association analysis of DNA markers independently developed from the Ma6 and Ma4 regions confirmed the mapping of Ma6 and Ma4. In the background of MaMa, 20.6% of acidity variation could be explained by Ma6, 28.5% by Ma4, and 50.7% by the combination of both. The effects of Ma6 and Ma4 in the background of Mama were also significant, but lower. These findings provide important genetic insight into high acidity in apple.
TssA–TssM–TagA interaction modulates type VI secretion system sheath-tube assembly in Vibrio cholerae
Authors: Stietz Maria Silvina , Liang Xiaoye , Li Hao , Zhang Xinran , Dong Tao G. 
Published: October 2020

AbstractThe type VI protein secretion system (T6SS) is a powerful needle-like machinery found in Gram-negative bacteria that can penetrate the cytosol of receiving cells in milliseconds by physical force. Anchored by its membrane-spanning complex (MC) and a baseplate (BP), the T6SS sheath-tube is assembled in a stepwise process primed by TssA and terminated by TagA. However, the molecular details of its assembly remain elusive. Here, we systematically examined the initiation and termination of contractile and non-contractile T6SS sheaths in MC-BP, tssA and tagA mutants by fluorescence microscopy. We observe long pole-to-pole sheath-tube structures in the non-contractile MC-BP defective mutants but not in the Hcp tube or VgrG spike mutants. Combining overexpression and genetic mutation data, we demonstrate complex effects of TssM, TssA and TagA interactions on T6SS sheath-tube dynamics. We also report promiscuous interactions of TagA with multiple T6SS components, similar to TssA. Our results demonstrate that priming of the T6SS sheath-tube assembly is not dependent on TssA, nor is the assembly termination dependent on the distal end TssA–TagA interaction, and highlight the tripartite control of TssA–TssM–TagA on sheath-tube initiation and termination.
Intermolecular channels direct crystal orientation in mineralized collagen
Authors: Xu YiFei , Nudelman Fabio , Eren E. Deniz , Wirix Maarten J. M. , Cantaert Bram , Nijhuis Wouter H. , Hermida-Merino Daniel , Portale Giuseppe , Bomans Paul H. H. , Ottmann Christian , Friedrich Heiner , Bras Wim , Akiva Anat , Orgel Joseph P. R. O. , Meldrum Fiona C. , Sommerdijk Nico 
Published: October 2020

AbstractThe mineralized collagen fibril is the basic building block of bone, and is commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ~2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. From in vitro mineralization studies with HAp, CaCO3 and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril.
Objective assessment of patellar maltracking with 3 T dynamic magnetic resonance imaging: feasibility of a robust and reliable measuring technique
Authors: Frings Jannik , Dust Tobias , Krause Matthias , Ohlmeier Malte , Frosch Karl-Heinz , Adam Gerhard , Warncke Malte , Maas Kai-Jonathan , Henes Frank Oliver 
Published: October 2020

AbstractPatellofemoral maltracking predisposes the patellofemoral joint to instability. The purpose of this study was to provide a reliable dynamic magnetic resonance imaging (MRI) measuring technique for patellofemoral maltracking, and to investigate the influence of anatomical risk factors (AF) on patellar maltracking. Ten patients (2 males,8 females, average 19 years) with clinical maltracking and 20 controls (10 males,10 females,average 28 years) were examined with a dynamic, multi-slice gradient-echo MRI sequence, during repetitive flexion(40°) and full extension, in an open-chain-active-movement. In a 30-s time frame three simultaneous transverse slices were acquired.
Dynamic mediolateral translation and dynamic tilt were measured at defined positions, by two independent examiners. Reproducibility was tested in a set of five knees. Common AFs for patellar maltracking (tibial-tuberosity-to-trochlear-groove-(TT-TG)-distances, trochlea-sulcus-angle, trochlea-sulcus-depth, lateral-trochlear-inclination and Caton-Deschamps-Index) were analyzed in consensus, using standard static MRI sequences. In patients, dynamic mediolateral translation was significantly greater in patients (12.4 ± 6.9 mm vs. − 0.1 ± 2.3 mm, p < 0.001) and the patella was positioned significantly more laterally (17.5 ± 6.9 mm vs. 3.1 ± 2.4 mm, p < 0.001) compared to controls. During movement, the patella tilted 16.3 ± 13.1° laterally in patients and 1.9 ± 4.3° medially in controls (dynamic tilt) (p < 0.002). All AFs were significantly different between patients and controls. Pathological TT-TG-distances, Caton-Deschamps-Indices and trochlea-sulcus-angles strongly correlated with dynamic patellar translation and dynamic patellar tilt (p < 0.001). In the patient population, the primary pathologies for maltracking were lateralized-tibial-tubercle (n = 5), trochlea dysplasia n = 2, patella alta (n = 3). Interrater-reliability for translation and tilt-measurement was excellent (0.971/0.976, 95% CIs 0.939–0.986/0.950–0.988). Dynamic MRI reliably differentiates between abnormal and physiological patellar tracking. Dynamic tracking and tilt strongly correlate with measurable AFs, which reinforces their clinical use and validates the presented technique.
Comparative study between deep learning and QSAR classifications for TNBC inhibitors and novel GPCR agonist discovery
Authors: Tsou Lun K. , Yeh Shiu-Hwa , Ueng Shau-Hua , Chang Chun-Ping , Song Jen-Shin , Wu Mine-Hsine , Chang Hsiao-Fu , Chen Sheng-Ren , Shih Chuan , Chen Chiung-Tong , Ke Yi-Yu 
Published: October 2020

AbstractMachine learning is a well-known approach for virtual screening. Recently, deep learning, a machine learning algorithm in artificial neural networks, has been applied to the advancement of precision medicine and drug discovery. In this study, we performed comparative studies between deep neural networks (DNN) and other ligand-based virtual screening (LBVS) methods to demonstrate that DNN and random forest (RF) were superior in hit prediction efficiency. By using DNN, several triple-negative breast cancer (TNBC) inhibitors were identified as potent hits from a screening of an in-house database of 165,000 compounds. In broadening the application of this method, we harnessed the predictive properties of trained model in the discovery of G protein-coupled receptor (GPCR) agonist, by which computational structure-based design of molecules could be greatly hindered by lack of structural information. Notably, a potent (~ 500 nM) mu-opioid receptor (MOR) agonist was identified as a hit from a small-size training set of 63 compounds. Our results show that DNN could be an efficient module in hit prediction and provide experimental evidence that machine learning could identify potent hits in silico from a limited training set.
Circadian regulation of diel vertical migration (DVM) and metabolism in Antarctic krill Euphausia superba
Authors: Piccolin Fabio , Pitzschler Lisa , Biscontin Alberto , Kawaguchi So , Meyer Bettina 
Published: October 2020

AbstractAntarctic krill (Euphausia superba) are high latitude pelagic organisms which play a key ecological role in the ecosystem of the Southern Ocean. To synchronize their daily and seasonal life-traits with their highly rhythmic environment, krill rely on the implementation of rhythmic strategies which might be regulated by a circadian clock. A recent analysis of krill circadian transcriptome revealed that their clock might be characterized by an endogenous free-running period of about 12–15 h. Using krill exposed to simulated light/dark cycles (LD) and constant darkness (DD), we investigated the circadian regulation of krill diel vertical migration (DVM) and oxygen consumption, together with daily patterns of clock gene expression in brain and eyestalk tissue. In LD, we found clear 24 h rhythms of DVM and oxygen consumption, suggesting a synchronization with photoperiod. In DD, the DVM rhythm shifted to a 12 h period, while the peak of oxygen consumption displayed a temporal advance during the subjective light phase. This suggested that in free-running conditions the periodicity of these clock-regulated output functions might reflect the shortening of the endogenous period observed at the transcriptional level. Moreover, differences in the expression patterns of clock gene in brain and eyestalk, in LD and DD, suggested the presence in krill of a multiple oscillator system. Evidence of short periodicities in krill behavior and physiology further supports the hypothesis that a short endogenous period might represent a circadian adaption to cope with extreme seasonal photoperiodic variability at high latitude.
Status of early hearing detection and intervention in South Korea: a nationwide population-based study of national infant health checkup
Authors: Park Su-Kyoung , Chang Jiwon , Im Gi Jung , Ahn Joong Ho , Lee Jun Ho , do Han Kyung , Chung Jong Woo , Kim Jin-Sook , Jang Hyunsook , Lee Seung Hwan 
Published: October 2020

AbstractThe aim of this study was to evaluate the status of early hearing detection and intervention after newborn hearing screening (NHS) in South Korea. A retrospective review of Korean national health insurance service data of all infants receiving the 4-month old national infant health checkup between 2010 and 2016 from a nationwide population-based database was conducted. Based on the results of the NHS-administered hearing questionnaires as part of the national infant health checkup, individuals were classified into “pass” (1,730,615 infants) or “refer” (10,941 infants) groups. Next, an analysis was conducted of age and the frequencies of tracking audiologic tests and surgeries of the middle ear (ME) and cochlear implants (CI). Diagnostic auditory brainstem response and audiometry, and surgeries of ME and CI were significantly performed more and earlier in the refer group compared with the pass group. For infants in the pass group who were presumed to have delayed or acquired hearing loss, the time of the first audiology tests and CI surgery was significantly delayed compared to those in the refer group; the average ages for first CI were 37 and 52 months in the refer group and pass group, respectively. Therefore, for early detection of delayed-onset hearing loss, regular hearing screening programs should be considered throughout the preschool ages.
Evidence for signatures of ancient microbial life in paleosols
Authors: Frindte Katharina , Lehndorff Eva , Vlaminck Stefan , Werner Katharina , Kehl Martin , Khormali Farhad , Knief Claudia 
Published: October 2020

AbstractLoess-paleosol sequences are terrestrial archives of past climate change. They may host traces of ancient microbial life, but little information is available on the recovery of microbial biomarkers from such deposits. We hypothesized that microbial communities in soil horizons up to an age of 127 kyr carry information related to past environments. We extracted DNA from a loess-paleosol sequence near Toshan, Northern Iran, with 26 m thick deposits showing different degrees of soil development, performed quantitative PCR and 16S rRNA gene amplicon sequencing. Periods of soil formation archived within the loess sediment led to higher diversity and bacterial abundance in the paleosol horizons. Community composition fluctuated over the loess-paleosol sequence and was mainly correlated with age and depth, (ADONIS R2 < 0.14, P ≤ 0.002), while responses to paleosol soil traits were weaker. Phyla like Bacteriodetes, Proteobacteria or Acidobacteria were more prevalent in paleosol horizons characterized by intense soil formation, while weakly developed paleosols or loess horizons hosted a higher percentage and diversity of Actinobacteria. Taken together, our findings indicate that the microbial community in loess-paleosol sequences carries signatures of earlier environmental conditions that are preserved until today.
Establishment and validation of an in vitro co-culture model for oral cell lines using human PBMC-derived osteoclasts, osteoblasts, fibroblasts and keratinocytes
Authors: Steller Daniel , Scheibert Alexandra , Sturmheit Tabea , Hakim Samer G. 
Published: October 2020

AbstractIndirect co-culture models with osteoclasts including oral cell lines may be influenced by M-CSF and RANKL in the common cell medium. Therefore, we investigated the viability and proliferation of osteoblasts (OB), fibroblasts (FB) and oral keratinocytes (OK) under stratified medium modification and assessed the differentiation of osteoclasts in each co-culture. The impact of M-CSF and RANKL in the common OC co-culture was assessed for OB, FB and OK via MTT assay via DAPI control. The multinuclearity and function of OC were evaluated by light microscopy, DAPI staining, resorption assay and FACS analysis. The PBMC showed the highest differentiation into OC after an incubation period of 7 days. Furthermore, co-culture with OB enhanced the number of differentiated multinucleated OC in comparison with monoculture, whereas co-culture with OK decreased PBMC multinuclearity and OC differentiation. FB did not influence the number of differentiated OC in a co-culture. RANKL and M-CSF reduction had no impact on OC differentiation in co-culture with FB or OB, whereas this medium modification for OK attenuated PBMC multinuclearity and OC differentiation in all approaches. Supplementation of RANKL and M-CSF can be modified for a co-culture of PBMC with FB or OB without disturbing OC differentiation. Thus, pathogenic processes of bone remodelling involving OB, OC, FB and OK in the oral cavity can be investigated thoroughly.
Post-inflammatory behavioural despair in male mice is associated with reduced cortical glutamate-glutamine ratios, and circulating lipid and energy metabolites
Authors: Chan Shi Yu , Probert Fay , Radford-Smith Daniel E. , Hebert Jennifer C. , Claridge Timothy D. W. , Anthony Daniel C. , Burnet Philip W. J. 
Published: October 2020

AbstractPost-inflammatory behaviours in rodents are widely used to model human depression and to test the efficacy of novel anti-depressants. Mice injected with lipopolysaccharide (LPS) display a depressive-like phenotype twenty-four hours after endotoxin administration. Despite the widespread use of this model, the mechanisms that underlie the persistent behavioural changes after the transient peripheral inflammatory response remain elusive. The study of the metabolome, the collection of all the small molecule metabolites in a sample, combined with multivariate statistical techniques provides a way of studying biochemical pathways influenced by an LPS challenge. Adult male CD-1 mice received an intraperitoneal injection of either LPS (0.83 mg/kg) or saline, and were assessed for depressive-like behaviour 24 h later. In a separate mouse cohort, pro-inflammatory cytokine gene expression and 1H nuclear magnetic resonance (NMR) metabolomics measurements were made in brain tissue and blood. Statistical analyses included Independent Sample t-tests for gene expression data, and supervised multi-variate analysis using orthogonal partial least squares discriminant analysis for metabolomics. Both plasma and brain metabolites in male mice were altered following a single peripheral LPS challenge that led to depressive-like behaviour in the forced swim test. The plasma metabolites altered by LPS are involved in energy metabolism, including lipoproteins, glucose, creatine, and isoleucine. In the brain, glutamate, serine, and N-acetylaspartate (NAA) were reduced after LPS, whereas glutamine was increased. Serine-modulated glutamatergic signalling and changes in bioenergetics may mediate the behavioural phenotype induced by LPS. In light of other data supporting a central imbalance of glutamate-glutamine cycling in depression, our results suggest that aberrant central glutaminergic signalling may underpin the depressive-like behaviours that result from both inflammation and non-immune pathophysiology. Normalising glutaminergic signalling, rather than seeking to increase serotonergic signalling, might prove to be a more coherent approach to the development of new treatments for mood disorder.
Sedimentary DNA tracks decadal-centennial changes in fish abundance
Authors: Kuwae Michinobu , Tamai Hiromichi , Doi Hideyuki , Sakata Masayuki K. , Minamoto Toshifumi , Suzuki Yoshiaki 
Published: October 2020

AbstractFar too little is known about the long-term dynamics of populations for almost all macro-organisms. Here, we examined the utility of sedimentary DNA techniques to reconstruct the dynamics in the “abundance” of a species, which has not been previously defined. We used fish DNA in marine sediments and examined whether it could be used to track the past dynamics of pelagic fish abundance in marine waters. Quantitative PCR for sedimentary DNA was applied on sediment-core samples collected from anoxic bottom sediments in Beppu Bay, Japan. The DNA of three dominant fish species (anchovy, sardine, and jack mackerel) were quantified in sediment sequences spanning the last 300 years. Temporal changes in fish DNA concentrations are consistent with those of landings in Japan for all three species and with those of sardine fish scale concentrations. Thus, sedimentary DNA could be used to track decadal-centennial dynamics of fish abundance in marine waters.
Caffeine inhibits Notum activity by binding at the catalytic pocket
Authors: Zhao Yuguang , Ren Jingshan , Hillier James , Lu Weixian , Jones Edith Yvonne 
Published: October 2020

AbstractNotum inhibits Wnt signalling via enzymatic delipidation of Wnt ligands. Restoration of Wnt signalling by small molecule inhibition of Notum may be of therapeutic benefit in a number of pathologies including Alzheimer’s disease. Here we report Notum activity can be inhibited by caffeine (IC50 19 µM), but not by demethylated caffeine metabolites: paraxanthine, theobromine and theophylline. Cellular luciferase assays show Notum-suppressed Wnt3a function can be restored by caffeine with an EC50 of 46 µM. The dissociation constant (Kd) between Notum and caffeine is 85 µM as measured by surface plasmon resonance. High-resolution crystal structures of Notum complexes with caffeine and its minor metabolite theophylline show both compounds bind at the centre of the enzymatic pocket, overlapping the position of the natural substrate palmitoleic lipid, but using different binding modes. The structural information reported here may be of relevance for the design of more potent brain-accessible Notum inhibitors.