bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonal and spatial variation in growth and abundance of zebra mussel (Dreissena polymorpha) in a recently invaded lake: implications for management
Authors: Rolla Matteo , Consuegra Sonia , Hall David J. , de Leaniz Carlos Garcia 
Published: June 2019

AbstractThe control of the highly invasive zebra mussel (Dreissena polymorpha) has been flagged as a priority but success has been variable. A better understanding of the growth and drivers of settlement of zebra mussel is necessary for a more efficient management of this invasive species, but seasonal data are still relatively scant. We monitored the seasonal changes in settlement rates, density, and growth of zebra mussel in artificial substrates over one year in Cardiff Bay (UK), an artificial amenity lake invaded by zebra mussels in 2003 and where the species is rapidly expanding. Mean settling rates varied from 4,200 to 6,200 mussel m−2over June to September mirroring changes in water temperature, and peaked at 17,960 mussels m−2, the highest density reported in Britain. Density was highest at the deepest panels (3 m). Growth varied significantly among sampling stations, with growth taking place during the summer and ceasing during winter and spring. Mixture analysis reveals the existence of multiple cohorts displaying different growth and settling rates and that follow different density dependent mechanisms, being positive density-dependent at low densities, and negative density-dependent at high densities. We suggest this creates the conditions necessary for source and sink metapopulations to develop which may need to be taken into account in management. Targeting mussels for removal in deep waters during the summer and early autumn might prove beneficial, but the existence of contrasting density-dependent mechanisms suggests that removal may be beneficial or counterproductive depending on local conditions.
Local translation of yeastERG4mRNA at the endoplasmic reticulum requires the brefeldin A resistance protein Bfr1
Authors: Manchalu Srinivas , Mittal Nitish , Spang Anne , Jansen Ralf-Peter 
Published: June 2019

ABSTRACTBrefeldin A resistance factor 1 (Bfr1p) is a non-essential RNA-binding protein and multi-copy suppressor of brefeldin A sensitivity inSaccharomyces cerevisiae. Deletion ofBFR1leads to multiple defects, including altered cell shape and size, change in ploidy, induction of P-bodies and chromosomal mis-segregation. Bfr1p has been shown to associate with polysomes, binds to several hundred mRNAs, and can target some of them to P-bodies. Although this implies a role of Bfr1p in translational control of mRNAs, its molecular function remains elusive. In the present study, we show that mutations in RNA-binding residues of Bfr1p impede its RNA-dependent co-localization with ER, yet do not mimic the known cellular defects seen uponBFR1deletion. However, a Bfr1 RNA-binding mutant is impaired in binding toERG4mRNA which encodes an enzyme required for the final step of ergosterol biosynthesis. Consistently,bfr1Δ strains show a strong reduction in Erg4p protein levels. Polysome profiling ofbfr1Δ orbfr1mutant strains reveals a strong shift ofERG4mRNA to polysomes, consistent with a function of Bfr1p in elongation. Collectively, our data reveal that Bfr1 has at least two separable functions: one in RNA-binding and elongation during translation, in particular at the ER membrane, and one in ploidy control or chromosome segregation.
Pleiotropy or linkage? Their relative contributions to the genetic correlation of quantitative traits and detection by multi-trait GWA studies
Authors: Chebib Jobran , Guillaume Frédéric 
Published: June 2019

AbstractGenetic correlations between traits may cause correlated responses to selection. Previous models described the conditions under which genetic correlations are expected to be maintained. Selection, mutation and migration are all proposed to affect genetic correlations, regardless of whether the underlying genetic architecture consists of pleiotropic or tightly-linked loci affecting the traits. Here, we investigate the conditions under which pleiotropy and linkage have differential effects on the genetic correlations between traits by explicitly modeling multiple genetic architectures to look at the effects of selection strength, degree of correlational selection, mutation rate, mutational variance, recombination rate, and migration rate. We show that at mutation-selection(-migration) balance, mutation rates differentially affect the equilibrium levels of genetic correlation when architectures are composed of pairs of physically linked loci compared to architectures of pleiotropic loci. Even when there is perfect linkage (no recombination within pairs of linked loci), a lower genetic correlation is maintained than with pleiotropy, with a lower mutation rate leading to a larger decrease. These results imply that the detection of causal loci in multi-trait association studies will be affected by the type of underlying architectures, whereby pleiotropic variants are more likely to be underlying multiple detected associations. We also confirm that tighter linkage between non-pleiotropic causal loci maintains higher genetic correlations at the traits and leads to a greater proportion of false positives in association analyses.
The CC′ loop of IgV domain containing immune checkpoint receptors: From a bystander to an active determinant of receptor:ligand binding
Authors: Kundapura Shankar V. , Ramagopal Udupi A. 
Published: June 2019

AbstractAntibodies targeting negative regulators of immune checkpoints have shown unprecedented and durable response against variety of malignancies. While the concept of blocking the negative regulators of immune checkpoints using mAbs appears to be an outstanding approach, their limited effect and several drawbacks such as resistance, poor solid tumor penetration and so on, calls for the rational design of next generation of therapeutics. Soluble isoforms of negative regulators of immune checkpoints are expressed naturally and are shown to regulate the immune response, suggesting the soluble version of these molecules and affinity-modified versions of these self-molecules could be effective lead molecules for immunotherapy. To get a better insight on hotspot regions for modification, we have analysed structures of available immune receptor:ligand complexes containing IgV domains. Interestingly, this analysis reveals that the CC′ loop of IgV domain, a loop which is distinct from CDRs which are generally utilized by antibodies to recognize antigens, plays a pivotal role in affinity modulation. Here, we present several examples of cognate partner specific conformational variation observed in CC′ loop of several checkpoint receptor:ligand complexes. In addition,in silicoswapping of CC′ loop targeting TIGIT:Nectin-2/PVR pathway corroborated well with biophysically determined affinity values for these complexes. Thus, CC′ loop appears to be a hotspot for affinity modification without affecting the specificity to their cognate receptors, an important requirement to avoid unintended interaction of these modified molecules with undesired targets.
Why did theTc1-like elements of mollusks acquired the spliceosomal introns?
Authors: Puzakov M.V. , Puzakova L.V. , Cheresiz S.V. 
Published: June 2019

AbstractTransposable elements are the DNA sequences capable of transpositions within the genome and, thus, exerting a considerable influence on the genome functioning and structure and providing the source of new genes. Transposable elements are classified into retrotransposons and the DNA transposons.IS630/Tc1/marinersuperfamily of DNA transposons is one of the most diverse groups broadly represented among the eukaryotes. We identified a new group ofTc1-like elements in the mollusks, which we namedTLEWI. These DNA transposons are characterized by the low copy number, the lack of terminal inverted repeats and the presence of DD36E signature and the spliceosomal introns in transposase sequence. Their prevalence among the mollusks is limited to subclass Pteriomorpha (Bivalvia). SinceTLEWIpossess the features of domesticated TE and the structure similar to the eukaryotic genes, which is not typical for the DNA transposons, we consider the hypothesis of co-optation ofTLEWIgene by the bivalves.
Pediatric High Grade Glioma Resources From the Children’s Brain Tumor Tissue Consortium (CBTTC) and Pediatric Brain Tumor Atlas (PBTA)
Authors: Ijaz Heba , Koptyra Mateusz , Gaonkar Krutika S. , Rokita Jo Lynne , Baubet Valerie P. , Tauhid Lamiya , Zhu Yankun , Brown Miguel , Lopez Gonzalo , Zhang Bo , Diskin Sharon J. , Vaksman Zalman ,   Children’s Brain Tumor Tissue Consortium, Mason Jennifer L. , Appert Elizabeth , Lilly Jena , Lulla Rishi , De Raedt Thomas , Heath Allison P. , Felmeister Alex , Raman Pichai , Nazarian Javad , Santi Maria Rita , Storm Phillip B. , Resnick Adam , Waanders Angela J. , Cole Kristina A. 
Published: June 2019

ABSTRACTBackgroundPediatric high grade glioma (pHGG) remains a fatal disease. Increased access to richly annotated biospecimens and patient derived tumor models will accelerate pHGG research and support translation of research discoveries. This work describes the pediatric high grade glioma set of the Children’s Brain Tumor Tissue Consortium (CBTTC) from the first release (October 2018) of the Pediatric Brain Tumor Atlas (PBTA).MethodspHGG tumors with associated clinical data and imaging were prospectively collected through the CBTTC and analyzed as the Pediatric Brain Tumor Atlas (PBTA) with processed genomic data deposited into PedcBioPortal for broad access and visualization. Matched tumor was cultured to create high grade glioma cell lines analyzed by targeted and WGS and RNA-seq. A tissue microarray (TMA) of primary pHGG tumors was also created.ResultsThe pHGG set included 87 collection events (73 patients, 60% at diagnosis, median age of 9 yrs, 55% female, 46% hemispheric). Analysis of somatic mutations and copy number alterations of known glioma genes were of expected distribution (36%H3.3, 47%TP53, 24%ATRXand 7%BRAFV600E variants). A pHGG TMA (n=77), includes 36 (53%) patient tumors with matched sequencing. At least one established glioma cell line was generated from 23 patients (32%). Unique reagents include those derived from aH3.3G34R glioma and from tumors with mismatch repair deficiency.ConclusionThe CBTTC and PBTA have created an openly available integrated resource of over 2,000 tumors, including a rich set of pHGG primary tumors, corresponding cell lines and archival fixed tissue to advance translational research for pHGG.IMPORTANCE OF STUDYHigh-grade gliomas (HGG) remain the leading cause of cancer death in children. Since molecularly heterogeneous, preclinical studies of pediatric HGG will be most informative if able to compare across groups. Given their relatively rarity, there are few readily available biospecimens and cellular models to inform preclinical laboratory and genomic translational research. Therefore, the aim of this CBTTC study was to highlight the panel of pediatric HGG cases whose primary tumors have undergone extensive genomic analysis, have clinical data, available imaging and additional biospecimens, including tumor, nucleic acids, cell lines and FFPE tissue on a tissue microarray (TMA).
Hybrid Refinement of Heterogeneous Conformational Ensembles using Spectroscopic Data
Authors: Hays Jennifer M. , Cafiso David S. , Kasson Peter M. 
Published: June 2019

ABSTRACTMulti-structured biomolecular systems play crucial roles in a wide variety of cellular processes but have resisted traditional methods of structure determination which often resolve only a few low-energy states. High-resolution structure determination using experimental methods that yield distributional data remains extremely difficult, especially when the underlying conformational ensembles are quite heterogeneous. We have therefore developed a method to integrate sparse, multi-multimodal spectroscopic data to obtain high-resolution estimates of conformational ensembles. We have tested our method by incorporating double electron-electron resonance data on the SNARE protein syntaxin-1a into biased molecular dynamics simulations. We find that our method substantially outperforms existing state-of-the-art methods in capturing syntaxin’s open/closed conformational equilibrium and further yields new conformational states that are both consistent with experimental data and may help in understanding syntaxin’s function. Our improved methods for refining heterogeneous conformational ensembles from spectroscopic data will greatly accelerate the structural understanding of such systems.
Gold Nanobipyramids as Second Near Infrared Optical Coherence Tomography Contrast Agents for Multiplexed In Vivo Lymphangiography
Authors: Si Peng , Shevidi Saba , Yuan Edwin , Yuan Ke , Lautman Ziv , Jeffrey Stefanie S. , Sledge George W. , de la Zerda Adam 
Published: June 2019

AbstractDeveloping contrast-enhanced optical coherence tomography (OCT) techniques is important for specific imaging of tissue lesions, molecular imaging, cell-tracking, and highly sensitive microangiography and lymphangiography. Multiplexed OCT imaging in the second near infrared (NIR-II) window is highly desirable since it allows simultaneous imaging and tracking of multiple biological events in high resolution with deeper tissue penetration in vivo. Here we demonstrate that gold nanobipyramids can function as OCT multiplexing contrast agents, allowing the visualization of two separate lymphatic flows occurring simultaneously from different drainage basins into the same lymph node in a live mouse. Contrast-enhanced multiplexed lymphangiography of a melanoma tumor in vivo shows that the peritumoral lymphatic drainage upstream of the tumor is unidirectional, with some drainage directly into the tumor, but the lymphatic drainage from the tumor is multi-directional. We also demonstrate real-time tracking of the contrast agents draining from a melanoma tumor specifically to the sentinel lymph node of the tumor and the three-dimensional distribution of the contrast agents in the lymph node.
Assessment of the in vitro function of human stem cell-derived β cells
Authors: Srivatsava Arvind R. , Shahan Stefanie T. , Gutgesell Lisa C. , Velazco-Cruz Leonardo , Millman Jeffrey R. 
Published: June 2019

AbstractInsulin-producing human embryonic stem cell-derived β (SC-β) cells are a promising cell source for diabetes cell replacement therapy. We have recently reported a differentiation strategy that produces SC-β cells in islet organoids that not only undergo glucose-stimulated insulin secretion but also have an islet-like dynamic insulin release profile, displaying both first and second phase insulin secretion. The goal of this study was to further characterize the functional profile of these SC-β cells in vitro. We utilized a Seahorse extracellular flux analyzer to measure mitochondrial respiration of SC-β cells at low and high glucose. We also used photolithography to fabricate a microfluidic device containing microwells to immobilize SC-β cells for perfusional analysis, monitoring cytoplasmic calcium using Fluo-4 AM at low and high glucose. Here we find that in addition to increased insulin secretion, SC-β cells have increased cellular respiration and cytoplasmic calcium ion concentration in response to a high glucose stimulation. Our results indicate that SC-β cells have similar function to that reported for islets, providing further performance characterization that could help with eventual development for diabetes cell therapy and drug screening.
Scanning SWATH acquisition enables high-throughput proteomics with chromatographic gradients as fast as 30 seconds
Authors: Messner Christoph B. , Demichev Vadim , Bloomfield Nic , White Matthew , Kreidl Marco , Ivosev Gordana , Wasim Fras , Zelezniak Aleksej , Lilley Kathryn S. , Tate Stephen , Ralser Markus 
Published: June 2019

AbstractBridging genotype to phenotype, the proteome has increasingly become of major importance to generate large, longitudinal sample series for data-driven biology and personalized medicine. Major improvements in laboratory automation, chromatography and software have increased the scale and precision of proteomics. So far missing are however mass spectrometric acquisition techniques that could deal with very fast chromatographic gradients. Here we present scanning SWATH, a data-independent acquisition (DIA) method, in which the DIA-typical stepwise windowed acquisition is replaced by a continuous movement of the precursor isolation window. Scanning SWATH accelerates the duty cycles to a few hundreds of milliseconds, and enables precursor mass assignment to the MS2 fragment traces for improving true positive precursor identification in fast proteome experiments. In combination with 800 µL/min high-flow chromatography, we report the quantification of 270 precursors per second, increasing the precursor identifications by 70% or more compared to previous methods. Scanning SWATH quantified 1,410 Human protein groups in conjunction with chromatographic gradients as fast as 30 seconds, 2,250 with 60-second gradients, and 4,586 in conjunction with 5-minute gradients. At high quantitative precision, our method hence increases the proteomic throughput to hundreds of samples per day per mass spectrometer. Scanning SWATH hence enables a broad range of new proteomic applications that depend on large numbers of cheap yet quantification precise proteomes.
Model-based analysis of response and resistance factors of cetuximab treatment in gastric cancer cell lines
Authors: Raimúndez Elba , Keller Simone , Zwingenberger Gwen , Ebert Karolin , Hug Sabine , Theis Fabian J. , Maier Dieter , Luber Birgit , Hasenauer Jan 
Published: June 2019

AbstractTargeted cancer therapies are powerful alternatives to chemotherapies or can be used complementary to these. Yet, the response to targeted treatments depends on a variety of factors, including mutations and expression levels, and therefore their outcome is difficult to predict. Here, we develop a mechanistic model of gastric cancer to study response and resistance factors for cetuximab treatment. The model captures the EGFR, ERK and AKT signaling pathways in two gastric cancer cell lines with different mutation patterns. We train the model using a comprehensive selection of time and dose response measurements, and provide an assessment of parameter and prediction uncertainties. We demonstrate that the proposed model facilitates the identification of causal differences between the cell lines. Furthermore, our study shows that the model provides accurate predictions for the responses to different perturbations, such as knockdown and knockout experiments. Among other results, the model predicted the effect of MET mutations on cetuximab sensitivity. These predictive capabilities render the model a powerful basis for the assessment of gastric cancer signaling and for the development and discovery of predictive biomarkers.Author SummaryUnraveling the causal differences between drug responders and non-responders is an important challenge. The information can help to understand molecular mechanisms and to guide the selection and design of targeted therapies. Here, we approach this problem for cetuximab treatment for gastric cancer using mechanistic mathematical modeling. The proposed model describes multiple gastric cancer cell lines and can accurately predict the response in several validation experiments. Our analysis provides a differentiated view on mutations and explains, for instance, the relevance of MET mutations and the insignificance of PIK3CA mutation in the considered cell lines. The model might provide the basis for understanding the recent failure of several clinical studies.
Biting rhythm, fecundity and longevity rate ofAedes albopictus(Skuse) females from different urbanized settings in Penang Island, Malaysia under uncontrolled laboratory conditions
Authors: Muhammad Nor Atikah Farhah , Kassim Nur Faeza Abu , Ab Majid Abdul Hafiz , Dieng Hamady , Avicor Silas Wintuma 
Published: June 2019

AbstractUrbanization could potentially modifyAedes albopictus’ecology by changing the dynamics of the species, and increasing the abundance of their breeding sites due to environmental changes, and thus contribute to dengue outbreaks. An efficient control of the vector requires a deeper understanding on the biological components of this vector. Thus, this study was conducted to evaluate the biting rhythm, fecundity and longevity rate ofAe. albopictusin relation to urbanization strata; urban, suburban and rural areas in Penang Island, Malaysia. The experiments were done in comparison to a laboratory strain. Twenty-four hours biting activity of all the mosquito strains showed a clear bimodal biting activity, with morning and evening twilight peaks. A two-way analysis of variance (ANOVA) found that there was statistically no significant interaction (F(69,192) = 1.337, P > 0.05) between the effects of biting time and mosquito strains. Meanwhile, fecundity rates were shown to be statistically significantly different between mosquito strains (F(3,442) = 10.559, P < 0.05) with urban areas having higher mean number of eggs (mean = 107.69, standard error = 3.98) than suburban (mean = 94.48, standard error = 5.18), and rural areas (mean = 72.52, standard error = 3.87). Longevity rates were significantly higher (F(3,441) = 31.259, P < 0.05) for mosquito strains from urban areas compared to the other strains. These findings would provide crucial and relevant fundamental information to the planning of control program in Malaysia, particularly Penang.Author SummaryAedes mosquito populations associated with human habitation in urban area do not only have the potential to cause biting nuisance, but also cause significant public health risks through the transmission of dengue virus. The socioeconomic effects of urbanization have been comprehensively studied by socio-ecologists, but the ecological effects and their impact on this vector biology was not known. The authors found that in Penang Island, the mean number of eggs laid per female ofAedes albopictusis high in the urban areas than those in suburban and rural areas. The survivorship is high for urban populations parallel to the fecundity rate and apparent biting pattern which is peak at dawn and dusk was noted for allAe. albopictusstrains. The changed environment in the urbanized area where more kinds of breeding containers and more blood sources produced by condensed human population supported by warm climate may facilitate larval development, enhance the vector survivorship and its reproductive fitness. These might be the reasons for quick adaptation and susceptibility ofAe. albopictusin urban areas. As higher fecundity rate and longer adult survival may enhance disease transmission, this species studied is indeed need high attention in terms of vector control.