bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Analysis of Tensor Tympani Muscle, Tympanic Diaphragm, Epitympanum, and Protympanum in Menière's Disease: a Human Temporal Bone Study
Authors: Azuma Takahiro , Nogaki Taketoshi , Schachern Patricia , Paparella Michael M. , Cureoglu Sebahattin 
Published: March 2018

Hypothesis:We hypothesized that there would be significant anatomic differences of the tensor tympani muscle (TTM), tympanic diaphragm, epitympanum, and protympanum in patients with versus without Menière's disease.Background:The effects of tenotomy on Menière's disease suggested it relieves the pressure on the inner ear of the contraction of the TTM and of negative middle ear pressure.Methods:Using human temporal bones from patients with Menière's disease, two studies were conducted. We examined the presence of otitis media, cholesteatoma, and endolymphatic hydrops, the length, diameter, configuration, the volume of the TTM and tendon, and the area of the tympanic isthmus (Study 1). We examined the presence of otitis media, cholesteatoma and endolymphatic hydrops, and the area and volume of the protympanum (Study 2).Results:In study 1, we observed no significant differences between the two groups. In study 2, we did not observe a small and narrow protympanum in the Menière's disease group. None of the ears in the Menière's or control groups had otitis media or cholesteatoma in either study. We observed hydrops in all the temporal bones of the Menière's disease group and none in the control groups.Conclusion:The position, configuration, and size of the tensor tympani muscle and tendon do not seem to play a role in the pathogenesis of Menière's disease. Because the tympanic isthmus and protympanum in Menière's disease are not smaller than controls and that none of the temporal bones had otitis media or cholesteatoma, it is unlikely that there was dysventilation in the middle ear.
Patterns of recurrence after curative-intent surgery for pancreas cancer reinforce the importance of locoregional control and adjuvant chemotherapy
Authors: Munir Rohan , Soreide Kjetil , Ravindran Rajan , Powell James J. , Harrison Ewen M. , Adair Anya , Wigmore Stephen J. , Parks Rowan W. , Garden O. James , Kirkpatrick Lorraine , Wall Lucy R , Christie Alan , Penman Ian , McAvoy Norma , Save Vicki , Stockman Alan , Worrall David , Ireland Hamish , Weir Graeme , Masson Neil , Hay Chris , Smith James-Gordon , Mole Damian J. 
Published: March 2018

AbstractIntroductionThe pattern of recurrence after surgical excision of pancreas cancer may guide alternative pre-operative strategies to either detect occult disease or need for chemotherapy. This study investigated patterns of recurrence after pancreatic surgery.MethodsRecurrence patterns were described in a series of resected pancreas cancers over a 2-year period and recurrence risk expressed as odds ratio (OR) with 95% confidence interval (C.I.). Survival was displayed by Kaplan-Meier curves.ResultsOf 107 pancreas resections, 69 (65%) had pancreatic cancer. R0 resection was achieved in 21 of 69 (30.4%). Analysis was based on 66 patients who survived 30 days after surgery with median follow up 21 months. Recurrence developed in 41 (62.1%) patients with median time to first recurrence of 13.3 months (interquartile range 6.9, 20.8 months). Recurrence site was most frequently locoregional (n=28, 42%), followed by liver (n=23, 35%), lymph nodes (n=21, 32%), and lungs (n=13, 19%). In patients with recurrence, 9 of 41 had single site recurrence; the remaining 32 patients had more than one site of recurrence. Locoregional recurrence was associated with R+ resection (53% vs 25% for R+ vs R0, respectively; OR 3.5, 95% C.I. 1.1-11.2; P=0.034). Venous invasion was associated with overall recurrence risk (OR 3.3, 95% C.I. 1.1-9.4; P=0.025). In multivariable analysis, R-stage and adjuvant chemotherapy predicted longer survival.DiscussionThe predominant locoregional recurrence pattern, multiple sites of recurrence and a high R+ resection rate reflect the difficulty in achieving initial local disease control.
MtMOT1.2 is responsible for molybdate supply toMedicago truncatulanodules
Authors: Gil-Díez Patricia , Tejada-Jiménez Manuel , León-Mediavilla Javier , Wen Jiangqi , Mysore Kirankumar S. , Imperial Juan , Gonzalez-Guerrero Manuel 
Published: March 2018

ABSTRACTSymbiotic nitrogen fixation in legume root nodules requires a steady supply of molybdenum for synthesis of the iron-molybdenum cofactor of nitrogenase. This nutrient has to be provided by the host plant from the soil, crossing several symplastically disconnected compartments through molybdate transporters, including members of the MOT1 family. MtMOT1.2 is aMedicago truncatulaMOT1 family member located in the endodermal cells in roots and nodules. Immunolocalization of a tagged MtMOT1.2 indicates that it is associated to the plasma membrane and to intracellular membrane systems, where it would be transporting molybdate towards the cytosol, as indicated in yeast transport assays. A loss-of-functionmot1.2-1mutant showed reduced growth compared to wild-type plants when nitrogen fixation was required, but not when nitrogen was provided as nitrate. While no effect on molybdenum-dependent nitrate reductase activity was observed, nitrogenase activity was severely affected, explaining the observed difference of growth depending on nitrogen source. This phenotype was the result of molybdate not reaching the nitrogen-fixing nodules, since genetic complementation with a wild-typeMtMOT1.2gene or molybdate-fortification of the nutrient solution, both restored wild-type levels of growth and nitrogenase activity. These results support a model in which MtMOT1.2 would mediate molybdate delivery by the vasculature into the nodules.
A novel xenograft model reveals invasive mesenchymal transition and ineffective angiogenic response during anti-angiogenic therapy resistance
Authors: Jahangiri Arman , Chen William , Chandra Ankush , Nguyen Alan , Yagnik Garima , Weiss Jacob , Wolf Kayla J. , Lin Jung-Ming G. , Mueller Soeren , Rick Jonathan , Sidorov Maxim , Flanigan Patrick , Carbonell W. Shawn , Diaz Aaron , Gilbert Luke , Kumar Sanjay , Aghi Manish K. 
Published: March 2018

ABSTRACTBevacizumab treatment of glioblastoma is limited by transient responses and acquired resistance. Because of the lengthy duration of treatment that can precede resistance in patients, in order to study changes underlying the evolution of bevacizumab resistance, we created a novel multigenerational xenograft model of acquired bevacizumab resistance. Glioblastoma xenografts were treated with bevacizumab or IgG, and the fastest growing tumor re-implanted into new mice, generating paired isogeneic responsive or resistant multigenerational xenografts. Microarray analysis revealed significant overexpression across generations of the mesenchymal subtype gene signature, paralleling results from patient bevacizumab-resistant glioblastomas (BRGs) that exhibited increasing mesenchymal gene expression correlating with increased bevacizumab treatment duration. Key mesenchymal markers, including YKL-40, CD44, SERPINE1, and TIMP1 were upregulated across generations, with altered morphology, increased invasiveness, and increased neurosphere formation confirmed in later xenograft generations. Interestingly, YKL-40 levels were elevated in serum of patients with bevacizumab-resistant vs. bevacizumab-naïve glioblastomas. Finally, despite upregulation of VEGF-independent pro-angiogenic genes across xenograft generations, immunostaining revealed increased hypoxia and decreased vessel density with increasing generation of treatment, mirroring our findings in patient BRGs and suggesting tumor growth despite effective devascularization caused by VEGF blockade. Besides identifying novel targets for preventing the evolution of resistance and offering a xenograft model for testing resistance inhibitors, our work suggests YKL-40 as a blood biomarker of bevacizumab resistance worthy of further evaluation.
Comprehensive Genetic Testing for Female and Male Infertility UsingNext Generation Sequencing
Authors: Patel Bonny , Parets Sasha , Akana Matthew , Kellogg Gregory , Jansen Michael , Chang Chihyu , Cai Ying , Fox Rebecca , Niknazar Mohammad , Shraga Roman , Hunter Colby , Pollock Andrew , Wisotzkey Robert , Jaremko Malgorzata , Bisignano Alex , Puig Oscar 
Published: March 2018

AbstractObjectiveTo develop a comprehensive genetic test for female and male infertility in support of medical decisions during assisted reproductive technology (ART) protocols.DesignRetrospective analysis of results from 118 DNA samples with known variants in loci representative of female and male infertility.Interventions(s)NoneMain Outcome Measure(s)Next-Generation Sequencing (NGS) of 87 genes including promoters, 5’ and 3’ untranslated regions, exons and selected introns. In addition, sex chromosome aneuploidies and Y chromosome microdeletions are analyzed concomitantly using the same panel.ResultsAnalytical accuracy was >99%, with >98% sensitivity for Single Nucleotide Variants (SNVs) and >91% sensitivity for insertions/deletions (indels). Clinical sensitivity was assessed with samples containing variants representative of male and female infertility, and it was 100% for SNVs/indels, CFTR IVS8-5T variants, sex chromosome aneuploidies and Copy Number Variants (CNVs), and >93% for Y chromosome microdeletions. Cost analysis comparing the NGS assay with standard, multiple analysis approach, shows potential savings of $2723 per case. Conclusion: A single, comprehensive, NGS panel can simplify the ordering process for healthcare providers, reduce turnaround time, and lower the overall cost of testing for genetic assessment of infertility in females and males, while maintaining accuracy.
Evidence for a unique DNA-dependent RNA polymerase in cereal crops
Authors: Trujillo Joshua T. , Seetharam Arun S. , Hufford Matthew B. , Beilstein Mark A. , Mosher Rebecca A. 
Published: March 2018

AbstractGene duplication is an important driver for the evolution of new genes and protein functions. Duplication of DNA-dependent RNA polymerase (Pol) II subunits within plants led to the emergence of RNA Pol IV and V complexes, each of which possess unique functions necessary for RNA-directed DNA Methylation. Comprehensive identification of Pol V subunit orthologs across the monocot radiation revealed a duplication of the largest two subunits within the grasses (Poaceae), including critical cereal crops. These paralogous Pol subunits display sequence conservation within catalytic domains, but their carboxy terminal domains differ in length and character of the Ago-binding platform, suggesting unique functional interactions. Phylogenetic analysis of the catalytic region indicates positive selection on one paralog following duplication, consistent with retention via neofunctionalization. Positive selection on residue pairs that are predicted to interact between subunits suggests that paralogous subunits have evolved specific assembly partners. Additional Pol subunits as well as Pol-interacting proteins also possess grass-specific paralogs, supporting the hypothesis that a novel Pol complex with distinct function has evolved in the grass family, Poaceae.
Graphical AbstractSignificance statementThe grass family is critically important for humans, as this group contains cereal grains such as rice, wheat, and corn that form the bulk of the human diet. Here we provide evidence that grasses have evolved a unique polymerase complex of unknown function, suggesting a novel mechanism of gene regulation in the grass lineage. In addition to implications for the biology of grasses, this system offers an opportunity to understand how evolution shapes multi-subunit complexes through duplication of individual components.
Ontogeny of familiarity with foraging landscape and foraging abilities in the tropical social waspRopalidia marginata
Authors: Mandal Souvik , Brahma Anindita , Gadagkar Raghavendra 
Published: March 2018

ABSTRACTPossessing spatial familiarity with their foraging landscape may enable animals to reduce foraging effort without compromising on foraging benefits. For animals inhabiting feature-rich landscapes, spatial familiarity can increase with increasing age/experience. To check whether this holds for individually foraging tropical social waspRopalidia marginata, we recorded the number and duration of all foraging trips, the identity of the materials brought to the nest (building material, water or food) and the directions of outbound and inbound flights (respective to their nests) of known-age foragers from three natural colonies, each for three consecutive days. The average trip duration and time spent daily in foraging increased rapidly until about first four weeks of their life, during which they rarely brought food to their nest, although many of them brought building material and water. Thereafter, their average as well as per day duration of foraging trip started decreasing gradually. Nevertheless, their foraging efficiency and success for food kept on increasing monotonically with age. These results suggest that older wasps were more efficient in foraging despite spending less time doing so. With increasing age, wasps developed individual preferences for the direction of their outbound flights, increased directionality of their inbound trips as well as the angular difference between their outbound and subsequent inbound flights, indicating development of spatial memory. We conclude that wasps acquire familiarity with their foraging landscape in their initial foraging phase and gradually develop robust memory for rewarding sites and routes to those sites, which enables them to increase their foraging capabilities.SUMMARY STATEMENTContrary to insects inhabiting less-featured landscapes, tropical social wasps invest weeks to get familiar with foraging landscapes during their early foraging lives. This eventually enables them to increase foraging gain with reduced effort.
Post-decision wagering after perceptual judgments reveals bi-directional certainty readouts
Authors: Moreira Caio M. , Rollwage Max , Kaduk Kristin , Wilke Melanie , Kagan Igor 
Published: March 2018

AbstractHumans and other animals constantly evaluate their decisions in order to learn and behave adaptively. Experimentally, such evaluation processes are accessed using metacognitive reports made after decisions, typically using verbally formulated confidence scales. When subjects report high confidence, it reflects a high certainty of being correct, but a low confidence might signify either low certainty about the outcome, or a high certainty of being incorrect. Hence, metacognitive reports might reflect not only different levels of decision certainty, but also two certainty directions (certainty of being correct and certainty of being incorrect). It is important to test if such bi-directional processing can be measured because, for decision-making under uncertainty, information about being incorrect is as important as information about being correct for guidance of subsequent behavior. We were able to capture implicit bi-directional certainty readouts by asking subjects to bet money on their perceptual decision accuracy using a six-grade wager scale (post-decision wagering, PDW). To isolate trial-specific aspects of metacognitive judgments, we used pre-decision wagering (wagering before the perceptual decision) to subtract, from PDW trials, influences resulting from non-trial-specific assessment of expected difficulty and psychological biases. This novel design allowed independent quantification of certainty of being correct and certainty of being incorrect, showing that subjects were able to read out certainty in a bi-directional manner. Certainty readouts about being incorrect were particularly associated with metacognitive sensitivity exceeding perceptual sensitivity (i.e. meta-d′ > d′), suggesting that such enhanced metacognitive efficiency is driven by information about incorrect decisions. Readouts of certainty in both directions increased on easier trials, and both certainty directions were also associated with faster metacognitive reaction times, indicating that certainty of being incorrect was not confounded with low certainty. Finally, both readouts influenced the amount of money subjects earned through PDW, suggesting that bi-directional readouts are important for planning future actions when feedback about previous decisions is unavailable.
A projection specific logic to sampling visual inputs in mouse superior colliculus
Authors: Reinhard Katja , Li Chen , Do Quan , Burke Emily , Heynderickx Steven , Farrow Karl 
Published: March 2018

AbstractUsing sensory information to trigger different behaviours relies on circuits that pass-through brain regions. However, the rules by which parallel inputs are routed to different downstream targets is poorly understood. The superior colliculus mediates a set of innate behaviours, receiving input from ~30 retinal ganglion cell types and projecting to behaviourally important targets including the pulvinar and parabigeminal nucleus. Combining transsynaptic circuit tracing with in-vivo and ex-vivo electrophysiological recordings we observed a projection specific logic where each collicular output pathway sampled a distinct set of retinal inputs. Neurons projecting to the pulvinar or parabigeminal nucleus uniquely sampled 4 and 7 cell types, respectively. Four others innervated both pathways. The visual response properties of retinal ganglion cells correlated well with those of their disynaptic targets. These findings suggest that projection specific sampling of retinal inputs forms a mechanistic basis for the selective triggering of visually guided behaviours by the superior colliculus.
Genetic recombination of poliovirus facilitates subversion of host barriers to infection
Authors: Acevedo Ashley , Woodman Andrew , Arnold Jamie J. , Yeh Ming Te , Evans David , Cameron Craig E. , Andino Raul 
Published: March 2018

AbstractThe contribution of RNA recombination to viral fitness and pathogenesis is poorly defined. Here, we isolate a recombination-deficient, poliovirus variant and find that, while recombination is detrimental to virus replication in tissue culture, recombination is important for pathogenesis in infected animals. Notably, recombination-defective virus exhibits severe attenuation following intravenous inoculation that is associated with a significant reduction in population size during intra-host spread. Because the impact of high mutational loads manifests most strongly at small population sizes, our data suggest that the repair of mutagenized genomes is an essential function of recombination and that this function may drive the long-term maintenance of recombination in viral species despite its associated fitness costs.Significance StatementRNA recombination is a widespread but poorly understood feature of RNA virus replication. For poliovirus, recombination is involved in the emergence of neurovirulent circulating vaccine-derived poliovirus, which has hampered global poliovirus eradication efforts. This emergence illustrates the power of recombination to drive major adaptive change; however, it remains unclear if these adaptive events represent the primary role of recombination in virus survival. Here, we identify a viral mutant with a reduced rate of recombination and find that recombination also plays a central role in the spread of virus within animal hosts. These results highlight a novel approach for improving the safety of live attenuated vaccines and further our understanding of the role of recombination in virus pathogenesis and evolution.
Femtomolar and selective dopamine detection by a gold nanoparticle enhanced surface plasmon resonance aptasensor
Authors: Cao Yong , McDermott Mark T. 
Published: March 2018

ABSTRACTUltrasensitive and selective detection and quantification of dopamine (DA) plays a key role in monitoring neurodegenerative diseases. However, the detection limit reported for DA detection is typically in the lower nM range. Pushing the detection limit to pM or lower for this particular target to cover the physiological levels (< 130 pM) is significant. Herein, DA DNA aptamer (DAAPT) gold nanoparticle (AuNP) conjugate is utilized to enhance the surface plasmon resonance (SPR) signal, which enables to detect and quantify DA in the femtomolar (200 fM) to picomolar range. To the best of our knowledge, this is the lowest detection limit achieved for SPR sensing of dopamine. The as-prepared 10 nm DAAPT-AuNP conjugate demonstrates strong binding affinity (Kd = 3.1 ± 1.4 nM) to the complementary DNA (cDNA) probe on gold chip. The cDNA probe is immobilized to the chip via polydopamine surface chemistry, which allows the Michael addition of any primary amine-terminated biomolecules. By adjusting the concentration of the DAAPT-AuNP conjugate, two calibration curves are generated with dynamic ranges from 100 µM to 2 mM, and from 200 fM to 20 nM, respectively. Both calibration curves have negative slopes, showing good agreement to a dose-response curve in an enzyme inhibition assay. In addition, the sensing strategy is evaluated to be specific for DA detection using a series of DA analogs and other metabolites as potential interferences.
Discordant attributes of structural and functional connectivity in a two-layer multiplex network
Authors: Lim Sol , Radicchi Filippo , van den Heuvel Martijn P , Sporns Olaf 
Published: March 2018

AbstractSeveral studies have suggested that functional connectivity (FC) is constrained by the underlying structural connectivity (SC) and mutually correlated. However, not many studies have focused on differences in the network organization of SC and FC, and on how these differences may inform us about their mutual interaction. To explore this issue, we adopt a multi-layer framework, with SC and FC, constructed using Magnetic Resonance Imaging (MRI) data from the Human Connectome Project, forming a two-layer multiplex network. In particular, we examine whether node strength assortativity within and between the SC and FC layer may confer increased robustness against structural failure. We find that, in general, SC is organized assortatively, indicating brain regions are on average connected to other brain regions with similar node strengths. On the other hand, FC shows disassortative mixing. This discrepancy is apparent also among individual resting-state networks within SC and FC. In addition, these patterns show lateralization, with disassortative mixing within FC subnetworks mainly driven from the left hemisphere. We discuss our findings in the context of robustness to structural failure, and we suggest that discordant and lateralized patterns of associativity in SC and FC may explain laterality of some neurological dysfunctions and recovery.