bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scanning electron microscopy-based screen of leaves ofSolanum pennellii(ac. LA716) xSolanum lycopersicum(cv. M82) introgression lines provides a resource for identification of loci involved in epidermal development in tomato
Authors: Galdon-Armero J. , Arce-Rodriguez M. L. , Martin C. 
Published: July 2019

AbstractThe aerial epidermis of plants plays a major role in their environment interactions, and the development of its cellular components -trichomes, stomata and pavement cells- is still not fully understood. We have performed a detailed screen of the leaf epidermis of two generations of the well-establishedSolanum pennelliiac. LA716 xSolanum lycopersicumcv. M82 introgression line (IL) population using a combination of scanning electron microscopy techniques. Quantification of the trichome and stomatal densities in the ILs revealed 18 genomic regions with a low trichome density and 4 ILs with a high stomatal density. We also found ILs with abnormal proportions of different trichome types and aberrant trichome morphologies. This work has led to the identification of new, unexplored genomic regions with roles in trichome and stomatal formation and provides an important dataset for further studies on tomato epidermal development that is publically available to the research community.
Simultaneous Targeting of XPO1 and BCL2 as an Effective Treatment Strategy for Double-Hit Lymphoma
Authors: Liu Yuanhui , Azizian Nancy G. , Dou Yaling , Pham Lan V. , Li Yulin 
Published: July 2019

AbstractDouble-hit lymphoma (DHL) is among the most aggressive and chemoresistant lymphoma subtypes. DHLs carry genomic abnormalities in MYC, BCL2 and/or BCL6 oncogenes. Due to simultaneous overexpression of these driver oncogenes, DHLs are highly resistant to the frontline therapies. Most DHLs overexpress both MYC and BCL2 driver oncogenes concurrently. We reasoned that simultaneous suppression of the two driver oncogenes would be more effective in eradicating DHLs than inactivation of single oncogene. XPO1 is a receptor for nuclear cytoplasmic transport of protein and RNA species. Recently, XPO1 inhibition was shown to downregulate MYC expression in several cancer cell lines. We therefore examined the role of XPO1 as a therapeutic target in suppressing MYC function and the potential synergistic effects of simultaneous suppression of XPO1 and BCL2 in the treatment of DHL. Here, we demonstrate that XPO1 inhibition abrogates MYC protein expression and induces massive tumor cell apoptosis. Combined use of XPO1 and BCL2 inhibitors is highly effective in eradicating DHL cells in cell culture. Notably, in a mouse model of DHL bearing primary tumor cells derived from lymphoma patients, combined treatment with XPO1 and BCL2 inhibitors blocks tumor progression, prevents brain metastasis, and extends host survival. Thus, our study confirms the simultaneous targeting of MYC and BCL2 driver oncogenes through the combined use of XPO1 and BCL2 inhibitors as a unique approach for the treatment of DHLs.
FAP57/WDR65 targets assembly of a subset of inner arm dyneins and connects to regulatory hubs in cilia
Authors: Lin Jianfeng , Le Thuc Vy , Augspurger Katherine , Tritschler Douglas , Bower Raqual , Fu Gang , Perrone Catherine , O’Toole Eileen T. , Mills Kristyn VanderWaal , Dymek Erin , Smith Elizabeth , Nicastro Daniela , Porter Mary E. 
Published: July 2019

AbstractCiliary motility depends on both the precise spatial organization of multiple dynein motors within the 96 nm axonemal repeat, and highly coordinated interactions between different dyneins and regulatory complexes located at the base of the radial spokes. Mutations in genes encoding cytoplasmic assembly factors, intraflagellar transport factors, docking proteins, dynein subunits, and associated regulatory proteins can all lead to defects in dynein assembly and ciliary motility. Significant progress has been made in the identification of dynein subunits and extrinsic factors required for pre-assembly of dynein complexes in the cytoplasm, but less is known about the docking factors that specify the unique binding sites for the different dynein isoforms on the surface of the doublet microtubules. We have used insertional mutagenesis to identify a new locus,IDA8/BOP2, required for targeting the assembly of a subset of inner dynein arms to a specific location in the 96 nm repeat.IDA8encodes FAP57/WDR65, a highly conserved WD repeat, coiled coil domain protein. Using high resolution proteomic and structural approaches, we find that FAP57 forms a discrete complex. Cryo-electron tomography coupled with epitope tagging and gold labeling reveal that FAP57 forms an extended structure that interconnects multiple inner dynein arms and regulatory complexes.
NMDAR-dependent emergence of behavioral representation in primary visual cortex
Authors: Puścian Alicja , Benisty Hadas , Higley Michael J. 
Published: July 2019

AbstractNeocortical sensory areas are generally thought to faithfully represent external stimuli. However, a growing body of evidence suggests that cortical networks exhibit considerable functional plasticity over multiple temporal scales, allowing them to modify their output to reflect ongoing behavioral demands. Nevertheless, the dynamics of sensory and non-sensory representations during acquisition of stimulus-guided behavior are not well understood. We performed longitudinal 2-photon imaging of activity in primary visual cortex (V1) of mice learning a conditioned eyeblink task. We found that both excitatory and inhibitory neurons robustly encode the visual stimulus throughout training despite a significant experience-dependent reduction in response magnitude. In contrast, both pyramidal neurons and parvalbumin-expressing interneurons exhibit emergence of behavioral representation during learning. The plasticity of visual response magnitude and behavioral representation is abolished following loss of NMDA-type glutamate receptors. Overall, our findings demonstrate that V1 networks can dynamically multiplex distinct behaviorally relevant representations over the course of learning.
Optimizing drug infusion schedules towards personalized cancer chronotherapy
Authors: Hill Roger J. W. , Innominato Pasquale F. , Lévi Francis , Ballesta Annabelle 
Published: July 2019

AbstractAimsPrecision medicine requires accurate technologies for drug administration and proper systems pharmacology approaches for patient data analysis. Here, plasma pharmacokinetics (PK) data of the OPTILIV trial in which cancer patients received oxaliplatin, 5-fluorouracil and irinotecan via chronomodulated schedules delivered by an infusion pump into the hepatic artery were mathematically investigated.MethodsA pump-to-patient model was designed in order to accurately represent the drug solution dynamics from the pump to the patient blood. It was connected to semi-mechanistic PK models to analyse inter-patient variability in PK parameters.ResultsLarge time delays of up to 1h41 between the actual pump start and the time of drug detection in patient blood was predicted by the model and confirmed by PK data. Sudden delivery spike in the patient artery due to glucose rinse after drug administration accounted for up to 10.7% of the total drug dose. New model-guided delivery profiles were designed to precisely lead to the drug exposure intended by clinicians. Next, the complete mathematical framework achieved a very good fit to individual time-concentration PK profiles and concluded that inter-subject differences in PK parameters was the lowest for irinotecan, intermediate for oxaliplatin and the largest for 5-fluorouracil. Clustering patients according to their PK parameter values revealed two patient subgroups for each drug in which inter-patient variability was largely decreased compared to that in the total population.ConclusionsThis study provides a complete mathematical framework to optimize drug infusion pumps and inform on inter-patient PK variability, a step towards precise and personalized cancer chronotherapy.Author summaryAccuracy and safety of infusion pumps remain a critical issue in the clinics and the development of accurate mathematical models to optimize drug administration though such devices has a key part to play in the advancement of precision medicine. Here, PK data from cancer patient receiving irinotecan, oxaliplatin and 5-fluorouracil into the hepatic artery via an infusion pump was mathematically investigated. A pump-to-patient model was designed and revealed significant inconsistencies between intended drug profiles and actual plasma concentrations. This mathematical model was then used to suggest improved profiles in order to minimise error and optimise delivery. Physiologically-based PK models of the three drugs were then linked to the pump-to-patient model. The whole framework achieved a very good fit to data and allowed quantifying inter-patient variability in PK parameters and linking them to potential clinical biomarkers via patient clustering. The developed methodology improves our understanding of patient-specific drug pharmacokinetics towards personalized drug administration.
Population codes of prior knowledge learned through environmental regularities
Authors: Quax Silvan C. , Bosch Sander E. , Peelen Marius V. , van Gerven Marcel A. J. 
Published: July 2019

ABSTRACTHow the brain makes correct inferences about its environment based on noisy and ambiguous observations, is one of the fundamental questions in Neuroscience. Prior knowledge about the probability with which certain events occur in the environment plays an important role in this process. Humans are able to incorporate such prior knowledge in an efficient, Bayes optimal, way in many situations, but it remains an open question how the brain acquires and represents this prior knowledge. The long time spans over which prior knowledge is acquired make it a challenging question to investigate experimentally. In order to guide future experiments with clear empirical predictions, we used a neural network model to learn two commonly used tasks in the experimental literature (i.e. orientation classification and orientation estimation) where the prior probability of observing a certain stimulus is manipulated. We show that a population of neurons learns to correctly represent and incorporate prior knowledge, by only receiving feedback about the accuracy of their inference from trial-to-trial and without any probabilistic feedback. We identify different factors that can influence the neural responses to unexpected or expected stimuli, and find a novel mechanism that changes the activation threshold of neurons, depending on the prior probability of the encoded stimulus. In a task where estimating the exact stimulus value is important, more likely stimuli also led to denser tuning curve distributions and narrower tuning curves, allocating computational resources such that information processing is enhanced for more likely stimuli. These results can explain several different experimental findings and clarify why some contradicting observations concerning the neural responses to expected versus unexpected stimuli have been reported and pose some clear and testable predictions about the neural representation of prior knowledge that can guide future experiments.
A digital collection of rare and endangered lemurs and other primates from the Duke Lemur Center
Authors: Yapuncich Gabriel S. , Kemp Addison D. , Griffith Darbi M. , Gladman Justin T. , Ehmke Erin , Boyer Doug M. 
Published: July 2019

AbstractScientific study of lemurs, a group of primates found only on Madagascar, is crucial for understanding primate evolution. Unfortunately, lemurs are among the most endangered animals in the world, so there is a strong impetus to maximize as much scientific data as possible from available physical specimens. MicroCT scanning efforts at Duke University have resulted in scans of more than 100 strepsirrhine cadavers representing 18 species from the Duke Lemur Center. Scans include specimen overviews and focused, high-resolution selections of complex anatomical regions (e.g., cranium, hands, feet). Scans have been uploaded to MorphoSource, an online digital repository for 3D data. As captive (but free ranging) individuals, these specimens have a wealth of associated information that is largely unavailable for wild populations, including detailed life history data. This digital collection maximizes the information obtained from rare and endangered animals without degradation of the original specimens.
Contributions to human breast milk microbiome and enteromammary transfer of Bifidobacterium breve
Authors: Kordy Kattayoun , Gaufin Thaidra , Mwangi Martin , Li Fan , Cerini Chiara , Lee David J. , Adisetiyo Helty , Woodward Cora , Pannaraj Pia S. , Tobin Nicole H. , Aldrovandi Grace M. 
Published: July 2019

AbstractIncreasing evidence supports the importance of the breast milk microbiome in seeding the infant gut. However, the origin of bacteria in milk and the process of milk microbe-mediated seeding of infant intestine need further elucidation. Presumed sources of bacteria in milk include locations of mother-infant and mother-environment interactions. We investigate the role of mother-infant interaction on breast milk microbes. Shotgun metagenomics and 16S rRNA gene sequencing identified milk microbes of mother-infant pairs in breastfed infants and in infants that have never latched. Although breast milk has low overall biomass, milk microbes play an important role in seeding the infant gut. Breast milk bacteria were largely comprised of Staphylococcus, Streptococcus, Acinetobacter, and Enterobacter primarily derived from maternal areolar skin and infant oral sites in breastfeeding pairs. This suggests that the process of breastfeeding is a potentially important mechanism for propagation of breast milk microbes through retrograde flux via infant oral and areolar skin contact. In one infant delivered via Caesarian section, a distinct strain of Bifidobacteria breve was identified in maternal rectum, breast milk and the infant’s stool potentially suggesting direct transmission. This may support the existence of microbial translocation of this anaerobic bacteria via the enteromammary pathway in humans, where maternal bacteria translocate across the maternal gut and are transferred to the mammary glands. Modulating sources of human milk microbiome seeding potentially imply opportunities to ultimately influence the development of the infant microbiome and health.
Injectable diblock copolypeptide hydrogel provides platform to maintain high local concentrations of taxol and local tumor control
Authors: Garrett Matthew C. , O’Shea Timothy M. , Wollenberg Alexander L. , Bernstein Alexander M. , Hung Derek , Staarman Brittany , Soto Horacio , Deming Timothy J. , Sofroniew Michael V. , Kornblum Harley I. 
Published: July 2019

AbstractIntroductionSurgical resection and systemic chemotherapy with temozolomide remain the mainstay for treatment of glioblastoma. However, many patients are not candidates for surgical resection given inaccessible tumor location or poor health status. Furthermore, despite being first line treatment, temozolomide has only limited efficacy.MethodsThe development of injectable hydrogel-based carrier systems allows for the delivery of a wide range of chemotherapeutics that can achieve high local concentrations, thus potentially avoiding systemic side effects and wide-spread neurotoxicity. To test this modality in a realistic environment, we developed a diblock copolypeptide hydrogel (DCH) capable of carrying and releasing paclitaxel, a compound that we found to be highly potent against primary gliomasphere cells.ResultsThe DCH produced minimal tissue reactivity and was well tolerated in the immune-competent mouse brain. Paclitaxel-loaded hydrogel induced less tissue damage, cellular inflammation and reactive astrocytes than cremaphor-taxol (typical taxol-carrier) or hydrogel alone. In a deep subcortical xenograft model, of glioblastoma in immunodeficient mice, injection of paclitaxel-loaded hydrogel led to a high local concentration of paclitaxel and led to local tumor control and improved survival. However, the tumor cells were highly migratory and were able to eventually escape the area of treatment.ConclusionsThese findings suggest this technology may be ultimately applicable to patients with deep-seated inoperable tumors, but as currently formulated, complete tumor eradication would be highly unlikely. Future studies should focus on targeting the migratory potential of surviving cells.
Effects of simulated acid rain on soil respiration rate and soil bacterial diversity in aPhyllostachyspubescensforest in subtropical China
Authors: Wang Nan , Pan Xiaocheng 
Published: July 2019

AbstractAcid rain has been regarded as a global environmental concern due to its negative effects on global ecosystems. In this study, we investigated the effects of simulated acid rain (SAR) on soil respiration rate and soil bacterial diversity in a Moso bamboo (phyllostachyspubescens) forest in subtropical China. Experimental results showed a similar seasonal pattern of soil respiration rates underdifferent SAR treatments. Seasonal mean soil respiration rates for CK (control, deionized water, pH 6.7), T1 (pH 5.6), T2 (pH 4.0) and T3 (pH 2.5) treatments were 3.44, 4.80, 4.35 and 4.51 μ mol m−2s−1, respectively. One-way analysis of variance indicated that the SAR exposure had no significant effect on soil respiration (p>0.1) and soil microbial biomass (p>0.1). Soil bacterial community diversity was calculated as the Shannon-Wiener diversity index and the results showed that only T3 treatment had significant effects on soil bacterial diversity. The DGGE analysis results revealed that T1 and CK soils had closer association and were related to the T2 soil, while T3 soil was distinctly different from the other treatments. This work highlights that the effects of SAR are important to consider in assessing the soil respiration rate, particularly under the scenario of increasing acid rain pollution.
Effects of a novel thermophilic cellulose-degrading agent on the quality of compost and change in microbial community of garden waste
Authors: Fan Zhouzhou , Jia Zhenzhen , Li Yongshuang , Lian Peng , Peng Xiawei 
Published: July 2019

AbstractKnowledge about the microbial communities in composting has advanced, but definitive knowledge concerning the application of actinomycetal communities in garden waste composting is still lacking. In this study, we compared the effects of amending compost with mixed agent M1 (five high-degradability strains) and other agents on the physicochemical indices and microbial community succession. The results showed that Pile A (only applying M1), exhibited a pH closer to neutral, the complete degradation of organic matter, and the highest remaining levels of nitrogen, phosphorus, and potassium. The seed germination rate, root length, and seed germination index values were significantly higher in piles amended with M1 and/or commercially available agents than in piles without exogenous microbial agents. Analyzing the microbial communities, these treatments were dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes during composting. The amount of Streptomyces was negatively correlated with the carbon/nitrogen ratio and positively correlated with total phosphorus and total potassium. Adding M1 increased microbial diversity, and the dominant microbial communities at the end of composting were similar to those found in the commercial microbial inoculum. Overall, agent M1 can shorten the composting process and increase the extent of degradation. This research provides additional insights into the potential function of Actinomycetes in compost ecology.
Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease
Authors: Okamoto Kinya , Koda Masahiko , Okamoto Toshiaki , Onoyama Takumi , Miyoshi Kenichi , Kishina Manabu , Matono Tomomitsu , Kato Jun , Tokunaga Shiho , Sugihara Takaaki , Hiramatsu Akira , Hyogo Hideyuki , Tobita Hiroshi , Sato Shuichi , Kawanaka Miwa , Hara Yuichi , Hino Keisuke , Chayama Kazuaki , Murawaki Yoshikazu , Isomoto Hajime 
Published: July 2019

AbstractIntroductionNon-alcoholic fatty liver disease (NAFLD) has a wide spectrum, eventually leading to cirrhosis and hepatic carcinogenesis. We previously reported that a series of microRNAs (miRNAs) mapped in the 14q32.2 maternally imprinted gene region (Dlk1-Dio3 mat) are related to NAFLD development and progression in a mouse model. We examined the suitability of miR-379, a circulating Dlk1-Dio3 mat miRNA, as a human NAFLD biomarker.MethodsEighty NAFLD patients were recruited for this study. miR-379 was selected from the putative Dlk1-Dio3 mat miRNA cluster because it exhibited the greatest expression difference between NAFLD and non-alcoholic steatohepatitis in our preliminary study. Real-time PCR was used to examine the expression levels of miR-379 and miR-16 as an internal control.ResultsCompared to normal controls, serum miR-379 expression was significantly up-regulated in NAFLD patients. Receiver operating characteristic curve analysis suggested that miR-379 is a suitable marker for discriminating NAFLD patients from controls, with an area under the curve value of 0.72. Serum miR-379 exhibited positive correlations with alkaline phosphatase, total cholesterol, and low-density-lipoprotein cholesterol levels in patients with early stage NAFLD (Brunt fibrosis stage 0 to 1). The correlation between serum miR-379 and cholesterol levels was lost in early stage NAFLD patients treated with statins. Software-based predictions indicated that various energy metabolism–related genes, including insulin-like growth factor-1 (IGF-1) and IGF-1 receptor, are potential targets of miR-379.ConclusionsSerum miR-379 exhibits high potential as a biomarker for NAFLD. miR-379 appears to increase cholesterol lipotoxicity, leading to the development and progression of NAFLD, via interference with the expression of target genes, including those related to the IGF-1 signaling pathway. Our results could facilitate future research into the pathogenesis, diagnosis, and treatment of NAFLD.