bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted phosphoproteomics of the Ras signaling network reveal regulatory mechanisms mediated by oncogenic KRAS
Authors: Urisman Anatoly , Yuan Tina L. , Trinidad Marena , Morris John H. , Afghani Shervin , Oses-Prieto Juan A. , Ritchie Cayde D. , Zahari Muhammad S. , Benes Cyril H. , Burlingame Alma L. , McCormick Frank 
Published: July 2019

AbstractBackgroundKRAS mutations are present in up to 30% of lung adenocarcinoma cases and are associated with poor survival. No effective targeted therapy against KRAS is currently available, and novel strategies to counteract oncogenic KRAS signaling are needed.ResultsWe used targeted proteomics to monitor abundance and site-specific phosphorylation in a network of over 150 upstream and downstream effectors of KRAS signaling in H358 cells (KRAS G12C). We compared patterns of protein regulation following sustained signaling blockade in the RAS/ERK module at two different levels, KRAS and MEK. Network-based analysis demonstrated complex non-linear patterns of regulation with wide-spread crosstalk among diverse subnetworks. Among 85 most regulated proteins in the network, only 12 proteins showed concordant regulation in response to signaling blockade at both KRAS and MEK levels, while the remainder were either specifically regulated in response to KRAS knockdown or MEK inhibition or showed orthogonal regulation in both conditions. Dephosphorylation of DNA methyltransferase 1 (DNMT1) at S714 was identified among the changes unique to KRAS knockdown, and here we elucidate the role of this phosphorylation in KRAS-dependent transcriptional silencing of tumor suppressor genes.ConclusionsNetwork-based analysis of the Ras signaling has shown complex non-linear patterns of regulation with wide-spread crosstalk among diverse subnetworks. Our work illustrates a targeted proteomics approach to functional interrogation of complex signaling networks focused on identification of readily testable hypotheses. These methods are widely applicable to diverse questions in tumor biology and other signaling paradigms.
Improving root characterisation for genomic prediction in cassava
Authors: Yonis Bilan Omar , del Carpio Dunia Pino , Wolfe Marnin , Jannink Jean-Luc , Kulakow Peter , Rabbi Ismail 
Published: July 2019

AbstractCassava is widely cultivated due to its high drought tolerance and high carbohydrate-containing storage roots. The lack of uniformity and irregular shape of storage roots within and between genotypes poses significant constraints on harvesting and post-harvest processing. Routine assessment of storage root size and shape in breeding plots relies on visual scores.Here, we phenotyped the Genetic gain and offspring (C1) populations from the International Institute of Tropical Agriculture (IITA) breeding program for root shape and size-related traits using image analysis of storage root photographs taken in the field.In our study, using univariate genome-wide association analysis, we detected for most shape and size related traits, significant QTL regions located on chromosomes 1 and 12. The QTL region on chromosome 12 has been previously associated, using IITA breeding populations, to cassava mosaic disease (CMD) resistance.Because the uniformity in size and shape of cassava roots is an important breeding goal, we calculated the standard deviation of individual root measurements per clone. The use of standard deviation measurements allowed the identification of new significant QTL for Perimeter, Feret and Aspect Ratio on chromosomes 6, 9 and 16. Using genomic prediction cross validation, the accuracies of root size and shape-related traits were lower than those previously reported for dry matter content (DM) and cassava mosaic virus resistance (CMD). Predictive accuracies of the mean values of root size and shape image-extracted traits were mostly higher than yield trait prediction accuracies in the C1 population. This study aimed to evaluate the feasibility of the image phenotyping protocol and to assess the use of genome-wide analyses for size and shape image-extracted traits. The methodology described here and the results obtained in this study are promising and open up the opportunity to apply high-throughput methods in cassava.
Z-scores unite >70 pairwise indices of ecological similarity and association for binary data
Authors: Keil Petr 
Published: July 2019

AbstractPairwise ecological resemblance, which includes compositional similarity between sites (beta diversity), or associations between species (co-occurrence), can be measured by >70 indices. Classical examples for presence-absence data are Jaccard index or C-score. These can be expressed using contingency table matching components a, b, c and d - the joint presences, presences at only one site/species, and joint absences. Using simulations of point patterns for two species with known magnitude of association, I demonstrate that most of the indices describe this simulated association almost identically, as long as they are calculated as a Z-score, i.e. as deviation of the index from a null expectation. Further, I show that Z-scores estimated resemblance better than raw forms of the indices, particularly in the face of confounding effects of spatial scale and conspecific aggregation. Finally, I show that any single of the matching components, when expressed as Z-score, can be used as an index that performs as good as the classical indices; this also includes joint absences. All this simplifies selection of the “right” resemblance index, it underscores the advantage of expressing resemblance as deviation from a null expectation, and it revives the potential of joint absences as a meaningful ecological quantity.
Sample delivery using capillary and delivery medium for serial crystallography
Authors: Nam Ki Hyun 
Published: July 2019

AbstractSerial crystallography (SX) is an innovative technology in structural biology that enables the visualization of molecular dynamics of macromolecules at room temperature. SX experiments always require a considerable amount of effort to deliver a crystal sample to the X-ray interaction point continuously and reliably. Here, a sample delivery method using a capillary and a delivery medium is introduced. The crystals embedded in the delivery medium can pass through the capillary tube, which is aligned with the X-ray beam, at very low flow rates without requiring elaborate delivery techniques and drastically reducing sample consumption. This simple but highly efficient sample delivery method can allow researchers to deliver crystals precisely to X-rays in SX experiments.
European common frog (Rana temporaria) recolonised Switzerland from multiple glacial refugia in northern Italy via trans- and circum-Alpine routes
Authors: Jansen van Rensburg A , Robin M , Phillips B C , Van Buskirk J 
Published: July 2019

AbstractThe high mountain ranges of western Europe have had a profound effect on the recolonisation of Europe from glacial refugia. The Alps present a particularly interesting case, because they present an absolute barrier to dispersal to most lineages, obstructing recolonisation from multiple refugia in the Italian Alps. Here we investigate the effect of the European Alps on the the phylogeographic history ofRana temporariaacross its range in Switzerland. Based on partialcytochrome bandCOX1sequences we find two mitochondrial lineages that occur roughly north and south of the alpine ridge bisecting Switzerland, with contact zones between them in the east and west. The northern haplogroup falls within the previously identified common western European haplogroup, while the southern haplogroup is unique to Switzerland. We find that the lineages diverged ~110 kya, approximately the onset of the last glacial maximum, indicative of origins in separate refugia. Phylogenetic analyses suggest that the lineages originate from two refugia in northern Italy, and colonised Switzerland via trans- and curcum-alpine routes. Our results show that the European Alps is a semi-permeable barrier to dispersal forR. temporaria, and have contributed to the complex recolonisation history of Switzerland.
Methods for Copy Number Aberration Detection from Single-cell DNA Sequencing Data
Authors: Fan Xian , Edrisi Mohammadamin , Navin Nicholas , Nakhleh Luay 
Published: July 2019

AbstractSingle-cell DNA sequencing technologies are enabling the study of mutations and their evolutionary trajectories in cancer. Somatic copy number aberrations (CNAs) have been implicated in the development and progression of various types of cancer. A wide array of methods for CNA detection has been either developed specifically for or adapted to single-cell DNA sequencing data. Understanding the strengths and limitations that are unique to each of these methods is very important for obtaining accurate copy number profiles from single-cell DNA sequencing data. Here we review the major steps that are followed by these methods when analyzing such data, and then review the strengths and limitations of the methods individually. In terms of segmenting the genome into regions of different copy numbers, we categorize the methods into three groups, select a representative method from each group that has been commonly used in this context, and benchmark them on simulated as well as real datasets. While single-cell DNA sequencing is very promising for elucidating and understanding CNAs, even the best existing method does not exceed 80% accuracy. New methods that significantly improve upon the accuracy of these three methods are needed. Furthermore, with the large datasets being generated, the methods must be computationally efficient.
Revisiting the landscape of evolutionary breakpoints across human genome using multi-way comparison
Authors: Vitae Golrokh , Remita Amine M. , Diallo Abdoulaye Baniré 
Published: July 2019

AbstractGenome rearrangement is one of the major forces driving the processes of the evolution and disease development. The chromosomal position affected by these rearrangements are called breakpoints. The breakpoints occurring during the evolution of species are known to be non randomly distributed. Detecting their landscape and mapping them to genomic features constitute an important features in both comparative and functional genomics. Several studies have attempted to provide such mapping based on pairwise comparison of genes as conservation anchors. With the availability of more accurate multi-way alignments, we design an approach to identify synteny blocks and evolutionary breakpoints based on UCSC 45-way conservation sequence alignments with 12 selected species. The multi-way designed approach with the mild flexibility of presence of selected species, helped to have a better determination of human lineage-specific evolutionary breakpoints. We identified 261,391 human lineage-specific evolutionary breakpoints across the genome and 2,564 dense regions enriched with biological processes involved in adaptive traits such asresponse to DNA damage stimulus, cellular response to stressandmetabolic process. Moreover, we found 230 regions refractory to evolutionary breakpoints that carry genes associated with crucial developmental process such asorgan morphogenesis, skeletal system development, chordate embryonic development, nerve developmentandregulation of biological process. This initial map of the human genome will help to gain better insight into several studies including developmental studies and cancer rearrangement processes.
Partial absence of PD-1 expression by tumor-specific CD8+T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report
Authors: Simoni Yannick , Becht Etienne , Li Shamin , Loh Chiew Yee , Yeong Joe Poh Sheng , Lim Tony Kiat Hon , Takano Angela , Tan Daniel S.W. , Newell Evan W. 
Published: July 2019

AbstractLymphoepithelioma-like carcinoma (LELC) is an uncommon lung cancer, typically observed in young, non-smoking Asian populations. LELC is associated with Epstein-Barr virus (EBV) infection of lung tumor cells of epithelial origin, suggesting a carcinogenic role of EBV as observed in nasopharyngeal carcinoma (NPC). Here, we studied the antigen specificity and phenotype of CD8+tumor infiltrating lymphocytes (TILs) in one LELC patient positive for EBV infection in lung tumor cells. Using MHC class I tetramers, we detected two populations of EBV-specific CD8+TILs, which can be considered as tumor-specific CD8+T cells, in the tumor of this patient. Transcriptomic analyses of these two populations reveal their distinct exhausted profiles and polyclonal TCR repertoire. High dimensional analyses at single cell level using mass cytometry showed showed that populations of tumor specific CD8+TILs are phenotypically heterogeneous, although they consistently express CD39. Unexpectedly, although the LELC tumor cells expressed abundant PD-L1, these tumor-specific CD8+TILs mostly did not express PD-1, suggesting that anti-PD1/PD-L1 immunotherapy may not be an appropriate strategy for disinhibiting EBV-specific cells for the treatment of LELC patients. These results might also help to explain low rates of checkpoint blockade immunotherapy response for NPC, despite the antigenicity of EBV for both tumor types.
The language network is recruited but not required for non-verbal event semantics
Authors: Ivanova Anna A. , Mineroff Zachary , Zimmerer Vitor , Kanwisher Nancy , Varley Rosemary , Fedorenko Evelina 
Published: July 2019

AbstractThe ability to combine individual meanings into complex representations of the world is often associated with language. Yet people also construct combinatorial event-level representations from non-linguistic input, e.g. from visual scenes. Here, we test whether the language network in the human brain is involved in and necessary for semantic processing of nonverbal events. In Experiment 1, we scanned participants with fMRI while they performed a semantic plausibility judgment task vs. a difficult perceptual control task on sentences and line drawings that describe/depict simple agent-patient interactions. We found that the language network responded robustly during the semantic task but not during the perceptual control task. This effect was observed for both sentences and pictures (although the response to sentences was stronger). Thus, language regions in healthy adults are engaged during a semantic task performed on pictorial depictions of events. But is this engagement necessary? In Experiment 2, we tested two individuals with global aphasia, who have sustained massive damage to perisylvian language areas and display severe language difficulties, against a group of age-matched control participants. Individuals with aphasia were severely impaired on a task of matching sentences and pictures. However, they performed close to controls in assessing the plausibility of pictorial depictions of agent-patient interactions. Overall, our results indicate that the left fronto-temporal language network is recruited but not necessary for semantic processing of nonverbal events.
Behavioral responses of the invasive flyPhilornis downsito stimuli from bacteria and yeast in the laboratory and the field in the Galapagos Islands
Authors: Yuval Boaz , Lahuatte Paola , Polpass Arul J. , Causton Charlotte , Jurkevitch Edouard , Kouloussis Nikolaus , Ben-Yosef Michael 
Published: July 2019

AbstractPhilornis downsi(Diptera: Muscidae) is a nest parasitic fly that has invaded the Galapagos archipelago and exerts an onerous burden on populations of endemic land birds. As part of an ongoing effort to develop tools for the integrated management of this fly, our objective was to determine its long and short-range responses to bacterial and yeast cues associated with adultP. downsi. We hypothesized that the bacterial and yeast communities will elicit attraction at distance through volatiles, and appetitive responses upon contact. Accordingly, we amplified bacteria from guts of adult field-caught individuals and bird feces, and yeasts from fermenting papaya juice (a known attractant ofP. downsi), on selective growth media, and assayed the response of flies to these microbes or their exudates. In the field, we baited traps with bacteria or yeast and monitored adult fly attraction. In the laboratory, we used the Proboscis Extension Response (PER) to determine the sensitivity of males and females to tarsal contact with bacteria or yeast. Long range trapping efforts yielded two female flies over 112 trap nights (one in extracts from bird faeces and one in extracts from gut bacteria from adult flies). In the laboratory, tarsal contact with bacterial stimuli from gut bacteria from adult flies elicited significantly more responses than did yeast stimuli. We discuss the significance of these findings in context with other studies in the field and identify targets for future work.
Co-evolutionary analysis accurately predicts details of interactions between the Integrator complex subunits
Authors: Fongang Bernard , Zhu Yingjie , Wagner Eric J. , Kudlicki Andrzej , Rowicka Maga 
Published: July 2019

ABSTRACTSolving the structure of large, multi-subunit complexes is difficult despite recent advances in cryoEM, due to remaining challenges to express and purify complex subunits. Computational approaches that predict protein-protein interactions, including Direct Coupling Analysis (DCA), represent an attractive alternative to dissect interactions within protein complexes. However, due to high computational complexity and high false positive rate they are applicable only to small proteins. Here, we present a modified DCA to predict residues and domains involved in interactions of large proteins. To reduce false positive levels and increase accuracy of prediction, we use local Gaussian averaging and predicted secondary structure elements. As a proof-of-concept, we apply our method to two Integrator subunits, INTS9 and INTS11, which form a heterodimeric structure previously solved by crystallography. We accurately predict the domains of INTS9/11 interaction. We then apply this approach to predict the interaction domains of two complexes whose structure is currently unknown: 1) The heterodimer formed by the Cleavage and Polyadenylation Specificity Factor 100-kD (CPSF100) and 73-kD (CPSF73); 2) The heterotrimer formed by INTS4/9/11. Our predictions of interactions within these two complexes are supported by experimental data, demonstrating that our modified DCA is a useful method for predicting interactions and can easily be applied to other complexes.
Compensatory mechanisms affect sensorimotor integration during ongoing vocal-motor acts in marmoset monkeys
Authors: Pomberger Thomas , Löschner Julia , Hage Steffen R. 
Published: July 2019

AbstractIn vertebrates, any transmission of vocal signals faces the challenge of acoustic interferences such as heavy rain, wind, animal, or urban sounds. Consequently, several mechanisms and strategies have evolved to optimize the signal-to-noise ratio. Examples to increase detectability are the Lombard effect, an involuntary rise in call amplitude in response to masking ambient noise, which is often associated with several other vocal changes such as call frequency and duration, as well as the animals’ capability of limiting calling to periods where noise perturbation is absent. Previous studies revealed rapid vocal flexibility and various audio-vocal integration mechanisms in marmoset monkeys. Using acoustic perturbation triggered by vocal behavior, we investigated whether marmoset monkeys are capable of exhibiting changes in call structure when perturbing noise starts after call onset or whether such effects only occur if noise perturbation starts prior to call onset. We show that marmoset monkeys are capable of rapidly modulating call amplitude and frequency in response to such perturbing noise bursts. Vocalizations swiftly increased call frequency after noise onset indicating a rapid effect of perturbing noise on vocal motor pattern production. Call amplitudes were also affected. Interestingly, however, the marmosets did not exhibit the Lombard effect as previously reported but decreased their call intensity in response to perturbing noise. Our findings indicate that marmosets possess a general avoidance strategy to call in the presences of ambient noise and suggest that these animals are capable of counteracting a previously thought involuntary audio-vocal mechanism, the Lombard effect, presumably via cognitive control processes.
G protein-coupled potassium channels implicated in mouse and cellular models of GNB1 Encephalopathy
Authors: Colombo Sophie , Petri Sabrina , Shalomov Boris , Reddy Haritha P. , Tabak Galit , Dhindsa Ryan S. , Gelfman Sahar , Teng Sasa , Krizay Daniel , Rafikian Elizabeth E. , Bera Amal K. , Yang Mu , Boland Michael J. , Peng Yueqing , Frankel Wayne N. , Dascal Nathan , Goldstein David B. 
Published: July 2019

SUMMARYDe novo mutations in GNB1, encoding the Gβ1 subunit of G proteins, cause a neurodevelopmental disorder with global developmental delay and epilepsy. Mice carrying a pathogenic mutation, K78R, recapitulate aspects of the disorder, including developmental delay and frequent spike-wave discharges (SWD). Cultured mutant cortical neurons display aberrant bursting activity on multi-electrode arrays. Strikingly, the antiepileptic drug ethosuximide (ETX) restores normal neuronal network behavior in vitro and suppresses SWD in vivo. In contrast, while valproic acid suppresses SWD, it does not restore normal network behavior, suggesting that ETX has mechanistic specificity for the effects of aberrant Gβ1 signaling. Consistent with this, we show that K78R is a gain-of-function of G protein-coupled potassium channel (GIRK) activation that is potently inhibited by ETX. This work suggests that altered Gβ1 signaling causes disease in part through effects on GIRK channels, illustrates the utility of cultured neuronal networks in pharmacological screening, and establishes effective pre-clinical models for GNB1 Encephalopathy.