bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolving definition of salivary gland stem cells
Authors: Rocchi Cecilia , Barazzuol Lara , Coppes Rob P. 
Published: February 2021

AbstractDysfunction of the salivary gland and irreversible hyposalivation are the main side effects of radiotherapy treatment for head and neck cancer leading to a drastic decrease of the quality of life of the patients. Approaches aimed at regenerating damaged salivary glands have been proposed as means to provide long-term restoration of tissue function in the affected patients. In studies to elucidate salivary gland regenerative mechanisms, more and more evidence suggests that salivary gland stem/progenitor cell behavior, like many other adult tissues, does not follow that of the hard-wired professional stem cells of the hematopoietic system. In this review, we provide evidence showing that several cell types within the salivary gland epithelium can serve as stem/progenitor-like cells. While these cell populations seem to function mostly as lineage-restricted progenitors during homeostasis, we indicate that upon damage specific plasticity mechanisms might be activated to take part in regeneration of the tissue. In light of these insights, we provide an overview of how recent developments in the adult stem cell research field are changing our thinking of the definition of salivary gland stem cells and their potential plasticity upon damage. These new perspectives may have important implications on the development of new therapeutic approaches to rescue radiation-induced hyposalivation.
Brain dynamics of (a)typical reading development—a review of longitudinal studies
Authors: Chyl Katarzyna , Fraga-González Gorka , Brem Silvia , Jednoróg Katarzyna 
Published: February 2021

AbstractLiteracy development is a process rather than a single event and thus should be studied at multiple time points. A longitudinal design employing neuroimaging methods offers the possibility to identify neural changes associated with reading development, and to reveal early markers of dyslexia. The core of this review is a summary of findings from longitudinal neuroimaging studies on typical and atypical reading development. Studies focused on the prediction of reading gains with a single neuroimaging time point complement this review. Evidence from structural studies suggests that reading development results in increased structural integrity and functional specialization of left-hemispheric language areas. Compromised integrity of some of these tracts in children at risk for dyslexia might be compensated by higher anatomical connectivity in the homologous right hemisphere tracts. Regarding function, activation in phonological and audiovisual integration areas and growing sensitivity to print in the ventral occipito-temporal cortex (vOT) seem to be relevant neurodevelopmental markers of successful reading acquisition. Atypical vOT responses at the beginning of reading training and infant auditory brain potentials have been proposed as neuroimaging predictors of dyslexia that can complement behavioral measures. Besides these insights, longitudinal neuroimaging studies on reading and dyslexia are still relatively scarce and small sample sizes raise legitimate concerns about the reliability of the results. This review discusses the challenges of these studies and provides recommendations to improve this research area. Future longitudinal research with larger sample sizes are needed to improve our knowledge of typical and atypical reading neurodevelopment.
Piglet immunization with a spike subunit vaccine enhances disease by porcine epidemic diarrhea virus
Authors: Yu Jieshi , Sreenivasan Chithra , Uprety Tirth , Gao Rongyuan , Huang Chen , Lee Ella J. , Lawson Steven , Nelson Julie , Christopher-Hennings Jane , Kaushik Radhey S. , Nelson Eric , Diel Diego G. , Hause Ben M. , Li Feng , Wang Dan 
Published: February 2021

AbstractImmunization with an insect cell lysate/baculovirus mixture containing recombinant porcine epidemic diarrhea virus (PEDV) spike protein induced high levels of neutralizing antibodies in both mice and piglets. However, immunization of piglets with this vaccine resulted in enhancement of disease symptoms and virus replication in vaccine recipients exposed to PEDV challenge. Thus, these observations demonstrate a previously unrecognized challenge of PEDV vaccine research, which has important implications for coronavirus vaccine development.
Texture-based markers from structural imaging correlate with motor handicap in Parkinson’s disease
Authors: Betrouni Nacim , Moreau Caroline , Rolland Anne-Sophie , Carrière Nicolas , Chupin Marie , Kuchcinski Gregory , Lopes Renaud , Viard Romain , Defebvre Luc , Devos David 
Published: February 2021

AbstractThere is a growing need for surrogate biomarkers for Parkinson’s disease (PD). Structural analysis using magnetic resonance imaging with T1-weighted sequences has the potential to quantify histopathological changes. Degeneration is typically measured by the volume and shape of morphological changes. However, these changes appear late in the disease, preventing their use as surrogate markers. We investigated texture changes in 108 individuals, divided into three groups, matched in terms of sex and age: (1) healthy controls (n = 32); (2) patients with early-stage PD (n = 39); and (3) patients with late-stage PD and severe L-dopa-related complications (n = 37). All patients were assessed in off-treatment conditions. Statistical analysis of first- and second-order texture features was conducted in the substantia nigra, striatum, thalamus and sub-thalamic nucleus. Regions of interest volumetry and voxel-based morphometry were performed for comparison. Significantly different texture features were observed between the three populations, with some showing a gradual linear progression between the groups. The volumetric changes in the two PD patient groups were not significantly different. Texture features were significantly associated with clinical scores for motor handicap. These results suggest that texture features, measured in the nigrostriatal pathway at PD diagnosis, may be useful in predicting clinical progression of motor handicap.
The role of tropical volcanic eruptions in exacerbating Indian droughts
Authors: Fadnavis Suvarna , Müller Rolf , Chakraborty Tanusri , Sabin T. P. , Laakso Anton , Rap Alexandru , Griessbach Sabine , Vernier Jean-Paul , Tilmes Simone 
Published: February 2021

AbstractThe Indian summer monsoon rainfall (ISMR) is vital for the livelihood of millions of people in the Indian region; droughts caused by monsoon failures often resulted in famines. Large volcanic eruptions have been linked with reductions in ISMR, but the responsible mechanisms remain unclear. Here, using 145-year (1871–2016) records of volcanic eruptions and ISMR, we show that ISMR deficits prevail for two years after moderate and large (VEI > 3) tropical volcanic eruptions; this is not the case for extra-tropical eruptions. Moreover, tropical volcanic eruptions strengthen El Niño and weaken La Niña conditions, further enhancing Indian droughts. Using climate-model simulations of the 2011 Nabro volcanic eruption, we show that eruption induced an El Niño like warming in the central Pacific for two consecutive years due to Kelvin wave dissipation triggered by the eruption. This El Niño like warming in the central Pacific led to a precipitation reduction in the Indian region. In addition, solar dimming caused by the volcanic plume in 2011 reduced Indian rainfall.
Diet and companionship modulate pain via a serotonergic mechanism
Authors: Tran Huy , Sagi Varun , Jarrett Sarita , Palzer Elise F. , Badgaiyan Rajendra D. , Gupta Kalpna 
Published: February 2021

AbstractTreatment of severe chronic and acute pain in sickle cell disease (SCD) remains challenging due to the interdependence of pain and psychosocial modulation. We examined whether modulation of the descending pain pathway through an enriched diet and companionship could alleviate pain in transgenic sickle mice. Mechanical and thermal hyperalgesia were reduced significantly with enriched diet and/or companionship. Upon withdrawal of both conditions, analgesic effects observed prior to withdrawal were diminished. Serotonin (5-hydroxytryptamine, 5-HT) was found to be increased in the spinal cords of mice provided both treatments. Additionally, 5-HT production improved at the rostral ventromedial medulla and 5-HT accumulated at the dorsal horn of the spinal cord of sickle mice, suggesting the involvement of the descending pain pathway in the analgesic response. Modulation of 5-HT and its effect on hyperalgesia was also investigated through pharmaceutical approaches. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, showed a similar anti-nociceptive effect as the combination of diet and companionship. Depletion of 5-HT through p-chlorophenylalanine attenuated the anti-hyperalgesic effect of enriched diet and companionship. More significantly, improved diet and companionship enhanced the efficacy of a sub-optimal dose of morphine for analgesia in sickle mice. These findings offer the potential to reduce opioid use without pharmacological interventions to develop effective pain management strategies.
Association of SLC6A4 methylation with long-term outcomes after stroke: focus on the interaction with suicidal ideation
Authors: Kang Hee-Ju , Lee Eun-Hye , Kim Ju-Wan , Kim Sung-Wan , Shin Il-Seon , Kim Joon-Tae , Park Man-Seok , Cho Ki-Hyun , Han Jung-Soo , Lyoo In Kyoon , Kim Jae-Min 
Published: February 2021

AbstractSerotonin (5-HT) plays an important role in cerebrovascular homeostasis and psychiatric disorders, including suicidality. Methylation of the serotonin transporter gene (SLC6A4) is associated with 5-HT expression. However, the prognostic roles of SLC6A4 methylation and suicidal ideation (SI) in long-term outcomes of stroke have not been evaluated. We investigated the independent and interactive effects of SLC6A4 methylation and SI immediately after stroke on long-term outcomes. Blood SLC6A4 methylation status and SI based on the suicide item of the Montgomery–Åsberg Depression Rating Scale were assessed in 278 patients at 2 weeks after stroke. After the index stroke, cerebro-cardiovascular events by SLC6A4 methylation status and SI were investigated over an 8–14-year follow-up period and using Cox regression models adjusted for a range of covariates. SLC6A4 hypermethylation and SI within 2 weeks of stroke both predicted worse long-term outcomes, independent of covariates. A significant interaction effect of SI and the methylation status of CpG 4 on long-term stroke outcomes was also identified. The association between SLC6A4 methylation and long-term adverse outcomes may be strengthened in the presence of SI within 2 weeks after stroke. Evaluation of methylation and SI status during the acute phase can be helpful when assessing stroke patients.
Adaptive hyperparameter updating for training restricted Boltzmann machines on quantum annealers
Authors: Xu Guanglei , Oates William S. 
Published: February 2021

AbstractRestricted Boltzmann Machines (RBMs) have been proposed for developing neural networks for a variety of unsupervised machine learning applications such as image recognition, drug discovery, and materials design. The Boltzmann probability distribution is used as a model to identify network parameters by optimizing the likelihood of predicting an output given hidden states trained on available data. Training such networks often requires sampling over a large probability space that must be approximated during gradient based optimization. Quantum annealing has been proposed as a means to search this space more efficiently which has been experimentally investigated on D-Wave hardware. D-Wave implementation requires selection of an effective inverse temperature or hyperparameter ($$\beta $$
β
) within the Boltzmann distribution which can strongly influence optimization. Here, we show how this parameter can be estimated as a hyperparameter applied to D-Wave hardware during neural network training by maximizing the likelihood or minimizing the Shannon entropy. We find both methods improve training RBMs based upon D-Wave hardware experimental validation on an image recognition problem. Neural network image reconstruction errors are evaluated using Bayesian uncertainty analysis which illustrate more than an order magnitude lower image reconstruction error using the maximum likelihood over manually optimizing the hyperparameter. The maximum likelihood method is also shown to out-perform minimizing the Shannon entropy for image reconstruction.
Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival
Authors: Singhal Sandeep K. , Byun Jung S. , Park Samson , Yan Tingfen , Yancey Ryan , Caban Ambar , Hernandez Sara Gil , Hewitt Stephen M. , Boisvert Heike , Hennek Stephanie , Bobrow Mark , Ahmed Md Shakir Uddin , White Jason , Yates Clayton , Aukerman Andrew , Vanguri Rami , Bareja Rohan , Lenci Romina , Farré Paula Lucia , De Siervi Adriana , Nápoles Anna María , Vohra Nasreen , Gardner Kevin 
Published: February 2021

AbstractThe use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso’s subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso’s role in breast cancer progression.
Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors
Authors: Yetsko Kelsey , Farrell Jessica A. , Blackburn Nicholas B. , Whitmore Liam , Stammnitz Maximilian R. , Whilde Jenny , Eastman Catherine B. , Ramia Devon Rollinson , Thomas Rachel , Krstic Aleksandar , Linser Paul , Creer Simon , Carvalho Gary , Devlin Mariana A. , Nahvi Nina , Leandro Ana Cristina , deMaar Thomas W. , Burkhalter Brooke , Murchison Elizabeth P. , Schnitzler Christine , Duffy David J. 
Published: February 2021

AbstractSea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression.Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. These conserved oncogenic drivers recapitulate remarkably well the core pan-cancer drivers responsible for human cancers. Fibropapillomatosis has been considered benign, but metastatic-related transcriptional signatures are strongly activated in kidney and established external tumors. Tumors in turtles with poor outcomes (died/euthanized) have genes associated with apoptosis and immune function suppressed, with these genes providing putative predictive biomarkers.Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, inter-tumor relationships, and therapeutic treatment for this wildlife epizootic.
Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction
Authors: Niemöller Christoph , Wehrle Julius , Riba Julian , Claus Rainer , Renz Nathalie , Rhein Janika , Bleul Sabine , Stosch Juliane M. , Duyster Justus , Plass Christoph , Lutsik Pavlo , Lipka Daniel B. , Lübbert Michael , Becker Heiko 
Published: February 2021

AbstractSingle-cell multi-omics are powerful means to study cell-to-cell heterogeneity. Here, we present a single-tube, bisulfite-free method for the simultaneous, genome-wide analysis of DNA methylation and genetic variants in single cells: epigenomics and genomics of single cells analyzed by restriction (epi-gSCAR). By applying this method, we obtained DNA methylation measurements of up to 506,063 CpGs and up to 1,244,188 single-nucleotide variants from single acute myeloid leukemia-derived cells. We demonstrate that epi-gSCAR generates accurate and reproducible measurements of DNA methylation and allows to differentiate between cell lines based on the DNA methylation and genetic profiles.
Synthesis and cytotoxic activity of unsaturated macrolides and their hybrid molecules with a C60 fullerene
Authors: Tuktarov Airat R. , Khuzina Liliya L. , Sadretdinova Zarema R. , Makarova Elina Kh. , Dzhemileva Lilya U. , D'yakonov Vladimir A. , Dzhemilev Usein M. 
Published: February 2021

Unreported macrodiolides containing a 1Z,5Z-diene fragment have been synthesized. Their hybrid molecules with C60 fullerene was found to significantly increase the cytotoxic effect (from 5 to 170 times) as compared to the initial macrodiolide.
MAGNUM survey: Compact jets causing large turmoil in galaxies
Authors: Venturi G. , Cresci G. , Marconi A. , Mingozzi M. , Nardini E. , Carniani S. , Mannucci F. , Marasco A. , Maiolino R. , Perna M. , Treister E. , Bland-Hawthorn J. , Gallimore J. 
Published: February 2021

Context. Outflows accelerated by active galactic nuclei (AGN) are commonly observed in the form of coherent, mildly collimated high-velocity gas directed along the AGN ionisation cones and kinetically powerful (≳1044 − 45 erg s−1) jets. Recent works found that outflows can also be accelerated by low-power (≲1044 erg s−1) jets, and the most recent cosmological simulations indicate that these are the dominant source of feedback on sub-kiloparsec scales, but little is known about their effect on the galaxy host.
Aims. We study the relation between radio jets and the distribution and kinematics of the ionised gas in IC 5063, NGC 5643, NGC 1068, and NGC 1386 as part of our survey of nearby Seyfert galaxies called Measuring Active Galactic Nuclei Under MUSE Microscope (MAGNUM). All these objects host a small-scale (≲1 kpc) low-power (≲1044 erg s−1) radio jet that has small inclinations (≲45°) with respect to the galaxy disc.
Methods. We employed seeing-limited optical integral field spectroscopic observations from the Multi Unit Spectroscopic Explorer (MUSE) at the Very Large Telescope to obtain flux, kinematic, and excitation maps of the extended ionised gas. We compared these maps with archival radio images and in one case, with Chandra X-ray observations.
Results. We detect a strong (up to ≳800–1000 km s−1) and extended (≳1 kpc) emission-line velocity spread perpendicular to the direction of the AGN ionisation cones and jets in all four targets. The gas excitation in this region of line-width enhancement is entirely compatible with shock ionisation. These broad and symmetric line profiles are not associated with a single coherent velocity of the gas. A ‘classical’ outflow component with net blueshifted and redshifted motions is also present, but is directed along the ionisation cones and jets.
Conclusions. We interpret the observed phenomenon as due to the action of the jets perturbing the gas in the galaxy disc. These intense and extended velocity spreads perpendicular to AGN jets and cones are indeed currently only observed in galaxies hosting a low-power jet whose inclination is sufficiently low with respect to the galaxy disc to impact on and strongly affect its material. In line with cosmological simulations, our results demonstrate that low-power jets are indeed capable of affecting the host galaxy.
Massive stars in the Small Magellanic Cloud
Authors: Bouret J.-C. , Martins F. , Hillier D. J. , Marcolino W. L. F. , Rocha-Pinto H. J. , Georgy C. , Lanz T. , Hubeny I. 
Published: February 2021

Context. The evolution of massive stars depends on several physical processes and parameters. Metallicity and rotation are among the most important, but their quantitative effects are not well understood.
Aims. To complement our earlier study on main-sequence stars, we study the evolutionary and physical properties of evolved O stars in the Small Magellanic Cloud (SMC). We focus in particular on their surface abundances to further investigate the efficiency of rotational mixing as a function of age, rotation, and global metallicity.
Methods. We analysed the UV and optical spectra of 13 SMC O-type giants and supergiants using the stellar atmosphere code CMFGEN to derive photospheric and wind properties. We compared the inferred properties to theoretical predictions from evolution models. For a more comprehensive analysis, we interpret the results together with those we previously obtained for O-type dwarfs.
Results. Most dwarfs of our sample lie in the early phases of the main sequence. For a given initial mass, giants are farther along the evolutionary tracks, which confirms that they are indeed more evolved than dwarfs. Supergiants have higher initial masses and are located past the terminal-age main-sequence in each diagram. We find no clear trend of a mass discrepancy, regardless of the diagram that was used to estimate the evolutionary mass. Surface CNO abundances are consistent with nucleosynthesis from the CNO cycle. Comparisons to theoretical predictions reveal that the initial mixture is important when the observed trends in the N/C versus N/O diagram are to be reproduced. A trend for stronger chemical evolution for more evolved objects is observed. Above about 30 M⊙, more massive stars are on average more chemically enriched at a given evolutionary phase. Below 30 M⊙, the trend vanishes. This is qualitatively consistent with evolutionary models. A principal component analysis of the abundance ratios for the whole (dwarfs and evolved stars) sample supports the theoretical prediction that massive stars at low metallicity are more chemically processed than their Galactic counterparts. Finally, models including rotation generally reproduce the surface abundances and rotation rates when different initial rotational velocities are considered. Nevertheless, for some objects, a stronger braking and/or more efficient mixing is required.