bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel molecules mediate specialized functions of human regulatory macrophages
Authors: Riquelme Paloma , Hutchinson James A. 
Published: July 2018

Purpose of review
Now that adoptive transfer of regulatory macrophages (Mregs) is clinically practicable, we ask whether this approach could be used to achieve self-sustaining peripheral regulation and what mechanisms may be involved.

Recent findings
Dehydrogenase/reductase 9 (DHRS9)-expressing Mregs are a specialized subset of monocyte-derived macrophages that are currently being investigated as a tolerogenic cell-based therapy. Human Mregs are defined by their capacity to convert naïve CD4+ T cells to IL-10-secreting FoxP3+ regulatory T cells (Tregs) through an activation-dependent process involving signals mediated by TGF-β, retinoic acid, indoleamine 2,3-dioxygenase activity, notch and progestagen associated endometrial protein (PAEP). Mreg-induced iTregs (miTregs) are a phenotypically distinct type of in-vitro-derived human iTreg that expresses butyrophilin-like protein 8 (BTNL8) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). miTregs are nonspecifically suppressive of mitogen-stimulated bystander T cell proliferation and inhibit TNFα-induced maturation of monocyte-derived dendritic cells. Preclinical and clinical studies find that intravenous infusion of allogeneic Mregs leads to enrichment of circulating TIGIT+ Tregs.

Summary
These results suggest a feed-forward mechanism by which Mreg treatment could promote solid organ transplant acceptance through rapid induction of direct pathway Tregs.
Case Managers on the Front Lines of Opioid Epidemic Response
Authors: Sortedahl Charlotte , Krsnak Jean , Crook Michelle M. , Scotton Lisa 
Published: July 2018

Purpose:
The purpose of this article is to examine how case managers, taking a holistic, patient-centered approach that is grounded in advocacy, have a crucial role to play in the opioid crisis response. This includes providing education, support, and resources to prevent misuse of and addiction to opioids prescribed for pain management and intervening with more resources to help combat the nonmedical use of prescription opioids and heroin.

Primary Practice Settings:
In addition to case managers in acute care, workers' compensation, and palliative care, who have frequent contact with patients who are prescribed opioid medications for pain management, all case managers may interact with patients and support systems/families who are directly or indirectly impacted by opioid use, misuse, and addiction.

Implementations for Case Management Practice:
The broad scope of the opioid epidemic necessitates individualized interventions to address the multiple needs of individuals. The case manager, particularly one who is board-certified, has the expertise and knowledge to assess individual needs, identify treatment and other resources, and provide education and support to the patient and family/support system. In addition, given the complexity and life-or-death consequences associated with the opioid crisis, a timely and comprehensive approach is essential, bringing together multiple disciplines in health care, public health, addiction, pain management, social work, mental health counseling, pharmacology, and case management.
Condyle Fractures: Impact of Surgical and Conservative Approaches on Oral Health
Authors: Magalhães Tibério Gomes , Andrade Gabriel Silva , Mello Manoel de Jesus Rodrigues , Carvalho Abrahão Cavalcante Gomes de Souza 
Published: July 2018

Abstract
The aim of this study is to assess the impact of oral health on the quality of life of patients who underwent conservative or surgical treatment for mandibular condylar fracture. A retrospective study was conducted, and 24 patients with condylar fracture were selected and underwent surgical or conservative treatment. Oral Health Impact Profile-14 (OHIP-14) was utilized to evaluate the patients. The angles of condylar fracture were measured in panoramic and Towne radiographs using the ImageJ software, and the results were compared to the results of the OHIP-14 questionnaire. Condylar fractures had a negative impact on the patients’ quality of life in pretreatment assessment. After conservative and surgical treatments, the condylar fracture had a low impact on the patients’ quality of life. Greater fracture alignment was obtained in patients treated by open reduction. A low level of correlation was observed between fracture alignment and changes in OHIP-14 of the patients studied. In conclusion, the study showed a significant improvement in the quality of life in the post-treatment period of the sample assessed. However, in patients selected for this study, no difference was found in the quality of life between the surgically and conservatively treated groups.
Central Retinal Artery Occlusion Due to Intraorbital Ophthalmic Artery Aneurysm
Authors: Carey Andrew R. 
Published: July 2018

Abstract:
A 60-year-old woman experienced sudden onset of vision loss in her right eye. Neuroimaging studies initially were interpreted as tumorous compression of the right optic nerve. On referral to our institution, examination findings were that of a right central retinal artery occlusion (CRAO). Review of the previous imaging studies was consistent with an aneurysm of the intraorbital ophthalmic artery at the origin of the central retinal artery, which was believed to be the cause of the CRAO.
Bio-optical properties and radiative energy budgets in fed and starved scleractinian corals (Pocillopora damicornis) during thermal bleaching
Authors: Lyndby Niclas Heidelberg , Holm Jacob Boiesen , Wangpraseurt Daniel , Ferrier-Pagès Christine , Kühl Michael 
Published: July 2018

AbstractCorals achieve outstanding photosynthetic quantum efficiencies approaching theoretical limits (i.e. 0.125 O2 photon-1) and it is unknown how such photosynthetic efficiency varies with environmental stress. In this study, we investigated the combined effects of thermal stress and active feeding on the radiative energy budget and photosynthetic efficiency of the symbiont-bearing coral Pocillopora damicornis by using fiber-optic and electrochemical microsensors in combination with variable chlorophyll fluorescence imaging. At normal temperature (25°C), the percentage of absorbed light energy used for photosynthesis was higher for fed (~5-6% under low light exposure) compared to unfed corals (4%). Corals from both feeding treatments responded equally to stress from high light exposure (2400 μmol photons m-2 s-1), exhibiting a decrease in photosynthetic energy efficiency down to 0.5-0.6%. Fed corals showed increased resilience against thermal bleaching compared to unfed corals, as fed corals were able to uphold their high photosynthetic energy efficiency for 5 days longer during thermal stress, as compared to unfed corals, which decreased their photosynthetic energy efficiency almost immediately when exposed to thermal stress. We conclude that active feeding is beneficial to corals by prolonging coral health and resilience during thermal stress as a result of an overall healthier symbiont population.
Monarch butterfly and milkweed declines substantially predate the use of genetically modified crops
Authors: Boyle JH , Dalgleish HJ , Puzey JR 
Published: July 2018

AbstractMonarch butterfly (Danaus plexippus) decline over the past 25 years has received considerable public and scientific attention, in large part because its decline, and that of its milkweed (Asclepias spp.) host plant, have been linked to genetically modified (GM) crops and the associated herbicide use. Therefore, the monarch has emerged as a poster child for the anti-GM movement. Here we use museum and herbaria specimens to extend our knowledge of the dynamics of both monarchs and milkweeds in the United States to more than a century, from 1900-2016. We show that monarch population trends closely follow those of their milkweed hosts; that both monarchs and milkweeds increased during the early 20th century, and that recent declines are actually part of a much longer term decline in both monarchs and milkweed beginning around 1950. Herbicide resistant crops, therefore, are clearly not the only culprit, and likely not even the primary culprit, as these declines began decades before GM crops were introduced.
Active intermixing of indirect and direct neurons builds the striatal mosaic
Authors: Tinterri Andrea , Menardy Fabien , Diana Marco A. , Lokmane Ludmilla , Keita Maryama , Coulpier Fanny , Lemoine Sophie , Mailhes Caroline , Mathieu Benjamin , Merchan-Sala Paloma , Campbell Kenneth , Gyory Ildiko , Grosschedl Rudolf , Popa Daniela , Garel Sonia 
Published: July 2018

AbstractThe striatum controls behaviors via the activity of direct and indirect pathway projection neurons (dSPN and iSPN) that are intermingled in all compartments. While such mosaic ensures the balanced activity of the two pathways, how it emerges remains largely unknown. Here, we show that both SPN populations are specified embryonically and progressively intermix through multidirectional iSPN migration. Using conditional mutants of the dSPN-specific transcription factor Ebf1, we found that inactivating this gene impaired selective dSPN properties, including axon pathfinding, whereas molecular and functional features of iSPN were preserved. Remarkably,Ebf1mutation disrupted iSPN/dSPN intermixing, resulting in an uneven distribution. Such architectural defect was selective of the matrix compartment, revealing that intermixing is a parallel process to compartment formation. Our study reveals that, while iSPN/dSPN specification is largely independent, their intermingling emerges from an active migration of iSPN, thereby providing a novel framework for the building of striatal architecture.
Uninterpretable interactions: epistasis as uncertainty
Authors: Sailer Zachary R. , Harms Michael J. 
Published: July 2018

AbstractEpistasis is a common feature of genotype-phenotype maps. Understanding the patterns of epistasis is critical for predicting unmeasured phenotypes, explaining evolutionary trajectories, and for inferring the biological mechanisms that determine a map. One common approach is to use a linear model to decompose epistasis into specific pairwise and high-order interactions between mutations. Such interactions are then used to identify important biology or to explain how the genotype-phenotype map shapes evolution. Here we show that the coefficients extracted from such analyses are likely uninterpretable. They cannot be extracted reliably from experimental genotype-phenotype maps due to regression bias. Further, we can generate epistatic “interactions” indistinguishable from those in experimental maps using a completely random process. From this, we conclude that epistasis should be treated as a random, but quantifiable, variation in these maps. This perspective allows us to build predictive models with known error from a small number of measured phenotypes. It also suggests that we need mechanistic, nonlinear models to account for epistasis and decompose genotype-phenotype maps.
Molecular dissection of early defense signaling underlying volatile-mediated defense priming and herbivore resistance in rice
Authors: Ye Meng , Glauser Gaétan , Lou Yonggen , Erb Matthias , Hu Lingfei 
Published: July 2018

AbstractHerbivore-induced plant volatiles prime plant defenses and resistance. How volatiles are integrated into early defense signaling is not well understood. Furthermore, whether there is a causal relationship between volatile defense priming and herbivore resistance is unclear. Here, we investigated the impact of indole, a common herbivore-induced plant volatile and known defense priming cue, on early defense signaling and herbivore resistance in rice. We show that rice plants infested bySpodoptera frugiperdacaterpillars release up to 25 ng*h−1. Exposure to equal doses of synthetic indole enhances rice resistance toS. frugiperda. Screening of early signaling components reveals that indole directly enhances the expression of the receptor like kinaseOsLRR-RLK1. Furthermore, indole specifically primes the transcription, accumulation and activation of the mitogen-activated protein kinaseOsMPK3as well as the expression of the downstream WRKY transcription factorOsWRKY70and several jasmonate biosynthesis genes, resulting in a higher accumulation of jasmonic acid (JA). Using transgenic plants defective in early signaling, we show thatOsMPK3is required, and thatOsMPK6andOsWRKY70contribute to indole-mediated defense priming of JA-dependent herbivore resistance. We conclude that volatiles can increase herbivore resistance of plants by priming early defense signaling components.
Using multiple measurements of tissue to estimate subject- and cell-type-specific gene expression
Authors: Wang Jiebiao , Devlin Bernie , Roeder Kathryn 
Published: July 2018

AbstractMotivationPatterns of gene expression, quantified at the level of tissue or cells, can inform on etiology of disease. There are now rich resources for tissue-level (bulk) gene expression data, which have been collected from thousands of subjects, and resources involving single-cell RNA-sequencing (scRNA-seq) data are expanding rapidly. The latter yields cell type information, although the data can be noisy and typically are derived from a small number of subjects.ResultsComplementing these approaches, we develop a method to estimate subject- and cell-type-specific (CTS) gene expression from tissue using an empirical Bayes method that borrows information across multiple measurements of the same tissue per subject (e.g., multiple regions of the brain). Analyzing expression data from multiple brain regions from the Genotype-Tissue Expression project (GTEx) reveals CTS expression, which then permits downstream analyses, such as identification of CTS expression Quantitative Trait Loci (eQTL).Availability and implementationWe implement this method as an R package MIND, hosted on https://github.com/randel/MIND.
Memory deficits in males and females long after subchronic immune challenge
Authors: Tchessalova Daria , Tronson Natalie C. 
Published: July 2018

ABSTRACTMemory impairments and cognitive decline persist long after recovery from major illness or injury, and correlate with increased risk of later dementia. Here we developed a subchronic peripheral immune challenge model to examine delayed and persistent memory impairments in females and in males. We show that intermittent injections of either lipopolysaccharide or Poly I:C cause memory decline in both sexes that are evident eight weeks after the immune challenge. Importantly, we observed sex-specific patterns of deficits. Females showed impairments in object recognition one week after challenge that persisted for at least eight weeks. In contrast, males had intact memory one week after the immune challenge but exhibited broad impairments in memory tasks including object recognition, and both context and tone fear conditioning several months later. The differential patterns of memory deficits in males and in females were observed without sustained microglial activation or changes in blood-brain barrier permeability. Together, these data suggest that transient neuroimmune activity results in differential vulnerabilities of females and males to memory decline after immune challenge. This model will be an important tool for determining the mechanisms in both sexes that contribute to memory impairments that develop over the weeks and months after recovery from illness. Future studies using this model will provide new insights into the role of chronic inflammation in the pathogenesis of long-lasting memory decline and dementias.
Chronic inflammatory pain drives alcohol drinking in a sex-dependent manner
Authors: Yu Waylin , Hwa Lara S. , Makhijani Viren H. , Besheer Joyce , Kash Thomas L. 
Published: July 2018

AbstractSex differences in chronic pain and alcohol abuse are not well understood. The development of rodent models is imperative for investigating the underlying changes behind these pathological states. However, past attempts have failed to produce drinking outcomes similar to those reported in humans. In the present study, we investigated whether hind paw treatment with the inflammatory agent Complete Freund’s Adjuvant (CFA) could generate hyperalgesia and alter alcohol consumption in male and female C57BL/6J mice. CFA treatment led to greater nociceptive sensitivity for both sexes in the Hargreaves test, and increased alcohol drinking for males in a continuous access two-bottle choice (CA2BC) paradigm. Regardless of treatment, female mice exhibited greater alcohol drinking than males. Following a 2-hour terminal drinking session, CFA treatment failed to produce changes in alcohol drinking, blood ethanol concentration (BEC), and plasma corticosterone (CORT) for both sexes. 2-hr alcohol consumption and CORT was higher in females than males, irrespective of CFA treatment. Taken together, these findings have established that male mice are more susceptible to escalations in alcohol drinking when undergoing pain, despite higher levels of total alcohol drinking and CORT in females. Furthermore, the exposure of CFA-treated C57BL/6J mice to the CA2BC drinking paradigm has proven to be a useful model for studying the relationship between chronic pain and alcohol abuse. Future applications of the CFA/CA2BC model should incorporate manipulations of stress signaling and other related biological systems to improve our mechanistic understanding of pain and alcohol interactions.
Weak electric fields promote resonance in neuronal spiking activity: analytical results from two-compartment cell and network models
Authors: Ladenbauer Josef , Obermayer Klaus 
Published: July 2018

AbstractTranscranial brain stimulation and evidence of ephaptic coupling have sparked strong interests in understanding the effects of weak electric fields on the dynamics of neuronal populations. While their influence on the subthreshold membrane voltage can be biophysically well explained using spatially extended neuron models, mechanistic analyses of neuronal spiking and network activity have remained a methodological challenge. More generally, this challenge applies to phenomena for which single-compartment (point) neuron models are oversimplified. Here we employ a pyramidal neuron model that comprises two compartments, allowing to distinguish basal-somatic from apical dendritic inputs and accounting for an extracellular field in a biophysically minimalistic way. Using an analytical approach we fit its parameters to reproduce the response properties of a canonical, spatial model neuron and dissect the stochastic spiking dynamics of single cells and large networks. We show that oscillatory weak fields effectively mimic anti-correlated inputs at the soma and dendrite and strongly modulate neuronal spiking activity in a rather narrow frequency band. This effect carries over to coupled populations of pyramidal cells and inhibitory interneurons, boosting network-induced resonance in the beta and gamma frequency bands. Our work contributes a useful theoretical framework for mechanistic analyses of population dynamics going beyond point neuron models, and provides insights on modulation effects of extracellular fields due to the morphology of pyramidal cells.Author SummaryThe elongated spatial structure of pyramidal neurons, which possess large apical dendrites, plays an important role for the integration of synaptic inputs and mediates sensitivity to weak extracellular electric fields. Modeling studies at the population level greatly contribute to our mechanistic understanding but face a methodological challenge because morphologically detailed neuron models are too complex for use in noisy, in-vivo like conditions and large networks in particular. Here we present an analytical approach based on a two-compartment spiking neuron model that can distinguish synaptic inputs at the apical dendrite from those at the somatic region and accounts for an extracellular field in a biophysically minimalistic way. We devised efficient methods to approximate the responses of a spatially more detailed pyramidal neuron model, and to study the spiking dynamics of single neurons and sparsely coupled large networks in the presence of fluctuating inputs. Using these methods we focused on how responses are affected by oscillatory weak fields. Our results suggest that ephaptic coupling may play a mechanistic role for oscillations of population activity and indicate the potential to entrain networks by weak electric stimulation.
Replicability of introgression under linked, polygenic selection
Authors: Sachdeva Himani , Barton Nicholas H. 
Published: July 2018

AbstractWe study how a block of genome with a large number of weakly selected loci introgresses under directional selection into a genetically homogeneous population. We derive exact expressions for the expected rate of growth of any fragment of the introduced block during the initial phase of introgression, and show that the growth rate of a single-locus variant is largely insensitive to its own additive effect, but depends instead on the combined effect of all loci within a characteristic linkage scale. The expected growth rate of a fragment is highly correlated with its long-term introgression probability in populations of moderate size, and can hence identify variants that are likely to introgress across replicate populations. We clarify how the introgression probability of an individual variant is determined by the interplay between hitchhiking with relatively large fragments during the early phase of introgression, and selection on fine scale variation within these, which at longer times results in differential introgression probabilities for beneficial and deleterious loci within successful fragments. By simulating individuals, we also investigate how introgression probabilities at individual loci depend on the variance of fitness effects, the net fitness of the introduced block, and the size of the recipient population, and how this shapes the net advance under selection. Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation.
Maintaining Gene Expression Levels by Positive Feedback in Burst Size in the Presence of Infinitesimal Delay
Authors: Bokes Pavol 
Published: July 2018

ABSTRACTSynthesis of individual molecules in the expression of genes often occurs in bursts of multiple copies. Gene regulatory feedback can affect the frequency with which these bursts occur or their size. Whereas frequency regulation has traditionally received more attention, we focus specifically on the regulation of burst size. It turns out that there are (at least) two alternative formulations of feedback in burst size. In the first, newly produced molecules immediately partake in feedback, even within the same burst. In the second, there is no within-burst regulation due to what we call infinitesimal delay. We describe both alternatives using a minimalistic Markovian drift-jump framework combining discrete and continuous dynamics. We derive detailed analytic results and efficient simulation algorithms for positive noncooperative autoregulation (whether infinitesimally delayed or not). We show that at steady state both alternatives lead to a gamma distribution of protein level. The steady-state distribution becomes available only after a transcritical bifurcation point is passed. Interestingly, the onset of the bifurcation is postponed by the inclusion of infinitesimal delay.