bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generic Quality of Life in Persons With Hearing Loss: A Review of the Recent Literature: RETRACTED
Authors: Brodie Arjuna , Ray Jaydip 
Published: August 2018

Background:
It is unknown whether persons with hearing loss (HL) have reduced generic quality of life (QoL) and to what extent a hearing aid (HA) might improve QoL. The main aim of the study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL.

Methods:
Literature databases (CINAHL, Pub Med, and Web of Science) were searched for relevant articles published from January 2000 to March 17, 2016. A primary search was performed regarding the relationship between HL, HA, and QoL (search one) followed by a supporting search about the relationship between distress/mood/anxiety and HL (search two). After removing duplications and screening the titles of the articles, the abstracts of the remaining articles were read and those that met the inclusion criteria were included.

Results:
The two searches yielded a total of 4,188 journal articles. Twenty journal articles were included in the present review: 13 from search one, and 7 from search two. The literature shows distressed persons tend to have a lowered generic QoL. Some studies suggest an improved generic QoL following the use of HA. Other studies suggest that HA use is one of several possible factors that contribute to improved generic QoL.

Conclusion:
Most of the studies suggest that HL is associated with reduced generic QoL. Using HA seems to improve general QoL. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship.
Surfactant Protein D Dampens Lung Injury by Suppressing NLRP3 Inflammasome Activation and NF-κB Signaling in Acute Pancreatitis
Authors: Yu Jia , Ni Lan , Zhang Xiaoyi , Zhang Jing , Abdel-Razek Osama , Wang Guirong 
Published: August 2018

ABSTRACT
Severe acute pancreatitis (SAP) often causes acute lung injury (ALI) by systemic inflammatory response. Surfactant protein D (SP-D) plays critical roles in host defense and inflammation regulation. NLRP3 inflammasomes and NF-κB signaling are key regulators in innate immunity and inflammation. We hypothesized that SP-D attenuates ALI by suppressing NLRP3 inflammasome and NF-κB activation.

Methods:
Wild-type C57BL/6 (WT), SP-D knockout (KO), and humanized transgenic SP-D (hTG) mice were used in this study. SAP was induced by administration of one-dose lipopolysaccharide (10 mg/kg) and 6 hourly intraperitoneal injections of cerulein (Cn) (100 μg/kg). Animals were killed 6 and 24 h after first Cn treatment. Histopathologic changes in pancreas and lung were assessed by light and electron microscopes. Serum amylase, IL-1β, IL-6, and MCP-1 levels were determined by kit/ELISA. NLRP3 inflammasome, NF-κB, and MPO activations were analyzed by western blotting and immunofluorescence.

Results:
KO mice showed more severe pancreatic and lung injury than WT mice in SAP. hTG mice exhibited similar degree in lung injury as WT mice. Mitochondrial and rough endoplasmic reticulum damages, autophagosome formation were observed in the alveolar type II and acinar cells of SAP mice. SAP KO mice had increased bronchoalveolar lavage fluid inflammatory cells, higher levels of serum IL-1β, IL-6, and MCP-1 than SAP WT and hTG mice. Levels of NLRP3 inflammasome (NLRP3, ASC, and Caspase-1) and NF-κB activation in SAP KO mice were higher than SAP WT and hTG mice.

Conclusion:
SP-D exerts protective effects against ALI via suppressing NLRP3 inflammasome and NF-κB activation in experimental SAP.
Whole blood mitigates the acute coagulopathy of trauma and avoids the coagulopathy of crystalloid resuscitation
Authors: Sheppard Forest R. , Schaub Leasha J. , Cap COL Andrew P. , Macko Antoni R. , Moore Hunter B. , Moore Ernest E. , Glaser CDR Jacob J. 
Published: August 2018

INTRODUCTION
The contributions of type and timing of fluid resuscitation to coagulopathy in trauma remain controversial. As part of a multifunctional resuscitation fluid research effort, we sought to further characterize the coagulation responses to resuscitation, specifically as compared to whole blood. We hypothesized that early whole blood administration mitigates the acute coagulopathy of trauma by avoiding the coagulopathy of CR resuscitation.

METHODS
Anesthetized rhesus macaques underwent polytraumatic, hemorrhagic shock, then a crossover study design resuscitation (n = 6 each) with either whole blood first (WB-1st) followed by crystalloid (CR); or CR-1st followed by WB. Resuscitation strategies were the following: WB-1st received 50% shed blood in 30minutes, followed by twice the shed blood volume (SBV) of CR over 30minutes and one times the SBV CR over 60minutes, where CR-1st received twice the SBV of CR over 30minutes, followed by 50% of shed blood in 30minutes, and one times the SBV CR over 60minutes. Blood samples were collected at baseline, end-of-shock, end-of-first and end-of-second resuscitation stages, and end-of-resuscitation for assessment (thromboelastometry, platelet aggregation, and plasmatic coagulation factors). Statistical analyses were conducted using two-way analysis of variance ANOVA with Bonferroni correction and t-tests; significance was at p < 0.05.

RESULTS
Survival, blood loss, hemodynamics, and shock duration were equivalent between the groups. Compared to baseline, parameters measured at first and second resuscitation stage time points directly following CR infusion revealed abnormalities in thromboelastometry (clot formation time, α angle, and maximum clot firmness), platelet aggregation response (to collagen, arachidonic acid, and adenosine diphosphate), and plasmatic coagulation (prothrombin time, anti-thrombin 3, and fibrinogen), while whole blood infusion resulted in stabilization or correction of these parameters following its administration.

CONCLUSIONS
These data suggest that in the setting of trauma and hemorrhagic shock, the coagulation alterations begin before intervention/resuscitation; however, these are significantly aggravated by CR resuscitation and could perhaps be best termed acute coagulopathy of resuscitation.
Study type: Translational animal model
Shear flow over flexible three-dimensional patches in a surface
Authors: Smith F. T. 
Published: August 2018

Slowly varying shear flow is considered over one or more flexible three-dimensional patches in a surface inside a boundary layer. At certain shear values, resonances emerge in which the effects on flow and patch shape are enlarged by an order of magnitude. Fast evolution then occurs: this leads to fully nonlinear unsteady interaction, after some delay, combining with finite-time break-ups to form a distinct path into transition.
This article is part of the theme issue ‘Modelling of sea-ice phenomena’.
Extreme copy number variation at a tRNA ligase affecting phenology and fitness in yellow monkeyflowers
Authors: Nelson Thom , Monnahan Patrick , McIntosh Mariah , Finseth Findley R. , Anderson Kayli , MacArthur-Waltz Evan , Kelly John K. , Fishman Lila 
Published: August 2018

AbstractCopy number variation (CNV) is a major part of the genetic diversity segregating within populations, but remains poorly understood relative to single nucleotide variation. Here, we report on a tRNA ligase gene (Migut.N02091; RLG1a) exhibiting unprecedented, and fitness-relevant, CNV within an annual population of the yellow monkeyflowerMimulus guttatus. RLG1a variation was associated with multiple traits in pooled population sequencing (PoolSeq) scans of phenotypic and phenological cohorts. Resequencing of inbred lines revealed intermediate frequency three-copy variants of RLG1a (trip+;5/35 = 14%), andtrip+lines exhibited elevated RLG1a expression under multiple conditions.trip+carriers, in addition to being over-represented in late-flowering and large-flowered PoolSeq populations, flowered later under stressful conditions in a greenhouse experiment (P < 0.05). In wild population samples, we discovered an additional rare RLG1a variant (high+)that carries 250-300 copies of RLG1a totaling ∼5.7Mb (20-40% of a chromosome). In the progeny of ahigh+carrier, Mendelian segregation of diagnostic alleles and qPCR-based copy counts indicate thathigh+is a single tandem array unlinked from the single copy RLG1a locus. In the wild,high+carriers had highest fitness in two particularly dry and/or hot years (2015 and 2017; both p < 0.01), while single copy individuals were twice as fecund as either CNV type in a lush year (2016: p < 0.005). Our results demonstrate fluctuating selection on CNVs affecting phenological traits in a wild population, suggest that plant tRNA ligases mediate stress-responsive life-history traits, and introduce a novel system for investigating the molecular mechanisms of gene amplification.
Regularization Improves the Robustness of Learned Sequence-to-Expression Models
Authors: Lunt Bryan , Sinha Saurabh 
Published: August 2018

AbstractUnderstanding of the gene regulatory activity of enhancers is a major problem in regulatory biology. The nascent field of sequence-to-expression modelling seeks to create quantitative models of gene expression based on regulatory DNA (cis) and cellular environmental (trans) contexts. All quantitative models are defined partially by numerical parameters, and it is common to fit these parameters to data provided by existing experimental results. However, the relative paucity of experimental data appropriate for this task, and lacunae in our knowledge of all components of the systems, results in problems often being under-specified, which in turn may lead to a situation where wildly different model parameterizations perform similarly well on training data. It may also lead to models being fit to the idiosyncrasies of the training data, without representing the more general process (overfitting).In other contexts where parameter-fitting is performed, it is common to apply regularization to reduce overfitting. We systematically evaluated the efficacy of three types of regularization in improving the generalizability of trained sequence-to-expression models. The evaluation was performed in two types of cross-validation experiments: one training on D. melanogaster data and predicting on orthologous enhancers from related species, and the other cross-validating between four D. melanogaster neurogenic ectoderm enhancers, which are thought to be under control of the same transcription factors. We show that training with a combination of noise-injection, L1, and L2 regularization can drastically reduce overfitting and improve the generalizability of learned sequence-to-expression models. These results suggest that it may be possible to mitigate the tendency of sequence-to-expression models to overfit available data, thus improving predictive power and potentially resulting in models that provide better insight into underlying biological processes.
Suppression of p16 induces mTORC1-mediated nucleotide metabolic reprogramming
Authors: Buj Raquel , Chen Chi-Wei , Dahl Erika S. , Leon Kelly E. , Kuskovsky Ross , Maglakelidze Natella , Navaratnarajah Maithili , Zhang Gao , Doan Mary T. , Jiang Helen , Zaleski Michael , Kutzler Lydia , Lacko Holly , Lu Yiling , Mills Gordan B. , Gowda Raghavendra , Robertson Gavin P. , Warrick Joshua I. , Herlyn Meenhard , Imamura Yuka , Kimball Scot R. , DeGraff David J. , Snyder Nathaniel W. , Aird Katherine M. 
Published: August 2018

SummaryReprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in reprogramming metabolism by increasing nucleotide synthesis. This occurred via activation of mTORC1 signaling, which directly mediated increased translation of the mRNA encoding ribose-5-phosphate isomerase A (RPIA), a pentose phosphate pathway enzyme. p16 loss correlated with activation of the mTORC1-RPIA axis in multiple cancer types. Suppression of RPIA inhibited proliferation only in p16-low cells by inducing senescence bothin vitroandin vivo. These data reveal the molecular basis whereby p16 loss modulates pro-tumorigenic metabolism through mTORC1-mediated upregulation of nucleotide synthesis and reveals a metabolic vulnerability of p16-null cancer cells.HighlightsmTORC1 is activated by p16 knockdown to increase nucleotide synthesis and bypass senescencemTORC1 directly increases translation RPIA to increase ribose-5-phosphateActivation of mTORC1 pathway downstream of p16 suppression is independent of RBRPIA suppression induces senescence only in cells and tumors with low p16
De novogenesis of retinal ganglion cells by targeted expression of KLF4in vivo
Authors: Rocha-Martins Maurício , Toledo Beatriz C. de , Santos-França Pedro L. , Oliveira-Valença Viviane M. , Vieira-Vieira Carlos H. , Matos-Rodrigues Gabriel E. , Linden Rafael , Norden Caren , Martins Rodrigo A. P. , Silveira Mariana S. 
Published: August 2018

AbstractRetinal ganglion cell (RGC) degeneration is a hallmark of glaucoma, the most prevalent cause of irreversible blindness. Thus, innovative therapeutic strategies are needed to protect and replace these projection neurons. It has been shown that endogenous glial cells of the retina, Müller cells, can be directly reprogrammed into late-born retinal interneurons. However, since RGCs are the first neurons born during development, the replacement of damaged RGCs requires the reprograming to an early neurogenic state. Here, we demonstrate that the pluripotency regulator Klf4 is sufficient to reprogram the potency of lineage-restricted retinal progenitor cells (RPCs) to generate RGCsin vivo. Transcriptome analysis disclosed that the overexpression of Klf4 induces crucial regulators of RGC competence and specification, including Atoh7 and Eya2. In contrast, loss-of-function studies in mice and zebrafish demonstrated that Klf4 is not essential for generation or differentiation of RGCs during retinogenesis. Nevertheless, induced RGCs (iRGCs) generated upon Klf4 overexpression migrate to the proper layer and project axons aligned with endogenous fascicles that reach the optic nerve head. Notably, iRGCs survive for up to 30 days afterin vivoreprogramming. Finally, we demonstrate that Klf4 converts Müller cells into neurons that express markers of RGCs. Altogether, we identified Klf4 as a promising tool to reprogram retinal cells and regenerate RGCs in the mature retina.Significance StatementCell fate determination is a key process for development, regeneration and for the design of therapeutic strategies that involve cellular reprogramming. This work shows that the manipulation of a single pluripotency regulator (Klf4) is sufficient to reprogram restricted progenitor cellsin vivo. These reprogrammed progenitors reacquire the potency to generate retinal ganglion cells. Ganglion cell degeneration is the leading cause of irreversible blindness; therefore, manipulation of ganglion cell competence is of relevance for human health. Our findings point to Klf4 as a promising tool to develop therapeutic strategies for the replacement of damaged ganglion cells.
Environmental DNA for the enumeration and management of Pacific salmon
Authors: Levi Taal , Allen Jennifer M. , Bell Donovan , Joyce John , Russell Joshua R. , Tallmon David A. , Vulstek Scott C. , Yang Chunyan , Yu Douglas W. 
Published: August 2018

AbstractPacific salmon are a keystone resource in Alaska, generating annual revenues of well over ∼US$500 million/yr. Due to their anadromous life history, adult spawners distribute amongst thousands of streams, posing a huge management challenge. Currently, spawners are enumerated at just a few streams because of reliance on human counters and, rarely, sonar. The ability to detect organisms by shed tissue (environmental DNA, eDNA) promises a more efficient counting method. However, although eDNA correlates generally with local fish abundances, we do not know if eDNA can accurately enumerate salmon. Here we show that daily, and near-daily, flow-corrected eDNA rate closely tracks daily numbers of returning sockeye and coho spawners and outmigrating sockeye smolts. eDNA thus promises accurate and efficient enumeration, but to deliver the most robust numbers will need higher-resolution stream-flow data, at-least-daily sampling, and a focus on species with simple life histories, since shedding rate varies amongst jacks, juveniles, and adults.
Ab initio derivation of the FRET equations resolves old puzzles and suggests measurement strategies
Authors: Raicu V. 
Published: August 2018

AbstractQuantitative FRET-based imaging methods rely on the determination of an apparent FRET efficiency (Eapp) as well as donor and acceptor concentrations, in order to uncover the identity and relative abundance of the oligomeric (or quaternary) structures of associating macromolecules. Theoretical work has provided “upwards” relationships between the experimentally determined Eapp distributions and the quaternary structure models that underlie them. By contrast, the body of work that predicates the “downwards” dependence of Eapp on directly measurable quantities (i.e., fluorescence emission of donors and acceptors) relies largely on plausibility arguments, one of which is the seemingly obvious assumption that the fraction of fluorescent molecules in the ground state pretty nearly equals the total concentration of molecules. In this work, we use the kinetic models of fluorescence in the presence and absence of FRET to rigorously derive useful relationships between Eapp and measurable fluorescence signals. Analysis of these relationships reveals a few anticipated surprises and some unexpected explanations for known experimental FRET puzzles, and it provides theoretical foundations for optimizing measurement strategies.
A non-dimensional, two-parameter mechanical model reveals alterations in nuclear mechanics upon Hepatitis C Virus infection
Authors: Balakrishnan Sreenath , Suma M S , Sharma Geetika , Raju Shilpa R , Reddy Uma , Das Saumitra , Ananthasuresh G. K. 
Published: August 2018

AbstractMorphology of the nucleus is an important regulator of gene-expression. Nuclear morphology is in turn a function of the forces acting on it and the mechanical properties of the nuclear envelope. Here, we present a two-parameter, non-dimensional mechanical model of the nucleus that reveals a relationship among nuclear shape parameters such as projected area, surface area and volume. Our model fits the morphology of individual nuclei and predicts the ratio between forces and modulus in each nucleus. We analyzed the changes in nuclear morphology of liver cells due to Hepatitis C Virus (HCV) infection using this model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in the pre-tension in cortical actin as the causes for the change in nuclear morphology. These predictions were validated biomechanically by showing that liver cells expressing HCV proteins possessed enhanced cellular stiffness and reduced nuclear stiffness. Concomitantly, cells expressing HCV proteins showed down-regulation of lamin-A,C and up-regulation of actin, corroborating the predictions of the model. Our modelling assumptions are broadly applicable to adherent, monolayer cell cultures making the model amenable to investigate changes in nuclear mechanics due to other stimuli by merely measuring nuclear morphology. Towards this, we present two techniques, graphical and numerical, to use our model for predicting physical changes in the nucleus.
A Note on Stochastic Modeling of Biological Systems: Automatic Generation of an Optimized Gillepsie Algorithm
Authors: Vanhaelen Quentin 
Published: August 2018

AbstractSignaling pathways and gene regulatory networks (GRNs) play a central role in the signal trans-duction and regulation of biochemical processes occurring within the cellular environment. Under-standing their mechanisms and dynamics is of major interest in various areas of life sciences and biological sciences. For example controlling stem cell fate decision requires a comprehension of the dynamical behavior of the networks involved in stem cell differentiation and pluripotency mainte-nance. In addition to analytical mathematical methods which are applicable for small or medium sized systems, there are many computational approaches to model and analyze the behavior of larger systems. However, from a dynamical point of view, modeling a combination of signaling pathways and GRNs present several challenges. Indeed, in addition to being of large dimensionality, these systems have specific dynamical features. Among the most commonly encountered is that the signal transduction controlled by the signaling pathways occurs at a different time scale than the transcription and translation processes. Also, stochasticity is known to strongly impact the regulation of gene expression. In this paper, we describe a simple implementation of an optimized version of the Gille-spie algorithm for simulating relatively large biological networks which include delayed reactions. The implementation presented herein comes with a script for automatically generating the different data structures and source files of the algorithm using standardized input files.Code availabilityThe Fortran90 implementation of the code and the R script described here as well as the tutorial with practical instructions are stored on the following github repository qvhaelen/ typhon
Conformational ensemble of the human TRPV3 ion channel
Authors: Zubcevic Lejla , Herzik Mark A. , Wu Mengyu , Borschel William F. , Hirschi Marscha , Song Albert , Lander Gabriel C. , Lee Seok-Yong 
Published: August 2018

SummaryTransient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin physiology through the release of pro-inflammatory messengers. Mutations in trpv3 have been identified as the cause of the congenital skin disorder, Olmsted syndrome. Unlike other members of the thermoTRPV channel family, TRPV3 sensitizes upon repeated simulation, yet a lack of structural information about the channel precludes a molecular-level understanding of TRPV3 sensitization and gating. Here, we present the cryo-electron microscopy structures of apo and sensitized human TRPV3, as well as several structures of TRPV3 in the presence of the common thermoTRPV agonist 2-aminoethoxydiphenyl borate (2-APB). Our results show α-to-π-helix transitions in the S6 during sensitization, and suggest a critical role for the S4-S5 linker π-helix during ligand gating.
DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP
Authors: Deshpande Rajashree A. , Myler Logan R. , Soniat Michael M. , Makharashvili Nodar , Lee Linda , Lees-Miller Susan P. , Finkelstein Ilya J. , Paull Tanya T. 
Published: August 2018

AbstractThe repair of DNA double-strand breaks occurs through non-homologous end joining or homologous recombination in vertebrate cells - a choice that is thought to be decided by a competition between DNA-dependent protein kinase (DNA-PK) and the Mre11/Rad50/Nbs1 (MRN) complex but is not well understood. Using ensemble biochemistry and single-molecule approaches, here we show that the MRN complex is dependent on DNA-PK and phosphorylated CtIP to perform efficient processing and resection of DNA ends in physiological conditions, thus eliminating the competition model. Endonucleolytic removal of DNA-PK-bound DNA ends is also observed at double-strand break sites in human cells. The involvement of DNA-PK in MRN-mediated end processing promotes an efficient and sequential transition from non-homologous end joining to homologous recombination by facilitating DNA-PK removal.One Sentence SummaryDNA-dependent protein kinase, an enzyme critical for non-homologous repair of DNA double-strand breaks, also stimulates end processing for homologous recombination.