bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmacytoid dendritic cells are functionally exhausted while non-haematopoietic sources of type I interferon dominate human autoimmunity
Authors: Psarras Antonios , Alase Adewonuola , Antanaviciute Agne , Carr Ian M. , Md Yusof Md Yuzaiful , Wittmann Miriam , Emery Paul , Tsokos George C. , Vital Edward M. 
Published: December 2018

ABSTRACTAutoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons (IFNs) have a crucial role in the progression to established autoimmune diseases such as systemic lupus erythematosus (SLE). However, their cellular source and regulation in disease initiation are unclear. The current paradigm suggests that plasmacytoid dendritic cells (pDCs) are activated in SLE contributing to excessive IFN production. Here, we show that in preclinical autoimmunity, established SLE, and primary Sjögren’s Syndrome, pDCs are not effector cells, but rather have lost their capacity for TLR-mediated IFN-α and TNF production and fail to induce T cell activation, independently of disease activity and blood IFN signature. In addition, pDCs present a transcriptional signature of cellular stress and senescence accompanied by increased telomere erosion. Instead, we demonstrate a marked enrichment of IFN signature in non-lesional skin in preclinical autoimmunity. In these individuals and SLE patients, type I IFNs were abundantly produced by keratinocytes in the absence of infiltrating leucocytes. These findings revise our understanding of the role of IFN in the initiation of human autoimmunity, with non-haematopoietic tissues perpetuating IFN responses, which in turn predict clinical disease. These data indicate potential therapeutic targets outside the conventional immune system for treatment and prevention.
The sensory coding of warm perception
Authors: Paricio-Montesinos Ricardo , Schwaller Frederick , Udhayachandran Annapoorani , Walcher Jan , Evangelista Roberta , Poulet James F.A. , Lewin Gary R. 
Published: December 2018

SummaryHumans easily discriminate tiny skin temperature changes that are perceived as warming or cooling. Dedicated thermoreceptors forming distinct thermosensory channels or “labelled lines” are thought to underlie thermal perception. We show that mice have similar perceptual thresholds for forepaw warming to humans (~1 °C change) and do not mistake warming for cooling. Mice perform warm discrimination tasks without dedicated thermoreceptors, but use information carried by unmyelinated polymodal C-fibers. Deletion of the heat-sensitive transduction channels TRPM2 and TRPV1 did not impact warming perception or afferent coding of warm. However, without the cold sensitive TRPM8 channel, afferent coding of cooling was impaired and these mice cannot perceive warming or cooling. Our data is incompatible with the existence of thermospecific labelled lines, but can be reconciled by the existence of central circuits that compare and integrate the input from at least two types of polymodal afferents, hitherto thought to exclusively signal pain.
The translatome of adult cortical axons is regulated by learning in vivo
Authors: Ostroff Linnaea E. , Santini Emanuela , Sears Robert , Deane Zachary , LeDoux Joseph E. , Lhakhang Tenzin , Tsirigos Aristotelis , Heguy Adriana , Klann Eric 
Published: December 2018

SummaryLocal translation can support memory consolidation by supplying new proteins to synapses undergoing plasticity. Translation in adult forebrain dendrites is an established mechanism of synaptic plasticity and is regulated by learning, yet there is no evidence for learning-regulated protein synthesis in adult forebrain axons, which have traditionally been believed to be incapable of translation. Here we show that axons in the adult rat amygdala contain translation machinery, and use translating ribosome affinity purification (TRAP) with RNASeq to identify mRNAs in cortical axons projecting to the amygdala, over 1200 of which were regulated during consolidation of associative memory. Mitochondrial and translation-related genes were upregulated, whereas synaptic, cytoskeletal, and myelin-related genes were downregulated; the opposite effects were observed in the cortex. Our results demonstrate that learning-regulated axonal translation occurs in the adult forebrain, and support the likelihood that local translation is more a rule than an exception in neuronal processes.
Alkane and wax ester production from lignin derived molecules
Authors: Salmela Milla , Lehtinen Tapio , Efimova Elena , Santala Suvi , Santala Ville 
Published: December 2018

AbstractLignin has potential as a sustainable feedstock for microbial production of industrially relevant molecules. However, the required lignin depolymerization yields a heterogenic mixture of aromatic monomers that are challenging substrates for the microorganisms commonly used in industry. Here, we investigated the properties of lignin-derived molecules (LDMs), namely coumarate, ferulate, and caffeate, in the synthesis of biomass and products in a LDM-utilizing bacterial hostAcinetobacter baylyiADP1. The biosynthesis products, wax esters and alkanes, are relevant compounds for the chemical and fuel industries. InA. baylyiADP1, wax esters are produced by a native pathway, whereas alkanes are produced by a synthetic pathway introduced to the host. Using individual LDMs as substrates, the growth, product formation, and toxicity to cells were monitored with internal biosensors. Of the tested LDMs, coumarate was the most propitious in terms of product synthesis. Wax esters were produced from coumarate with a yield and titer of 40 mg /gcoumarateand 221 mg/L, whereas alkanes were produced with a yield of 62.3 μg /gcoumarateand titer of 152 μg/L. This study demonstrates the microbial preference for certain LDMs, and highlights the potential ofA. baylyiADP1 as a convenient host for LDM upgrading to value-added products.
Evolution of metabolic novelty: a trichome-expressed invertase creates specialized metabolic diversity in wild tomato
Authors: Leong Bryan J. , Lybrand Daniel , Lou Yann-Ru , Fan Pengxiang , Schilmiller Anthony L. , Last Robert L. 
Published: December 2018

AbstractPlants produce myriad taxonomically restricted specialized metabolites. This diversity – and our ability to correlate genotype with phenotype – makes the evolution of these ecologically and medicinally important compounds interesting and experimentally tractable. Trichomes of tomato and other nightshade family plants produce structurally diverse protective compounds termed acylsugars. While cultivated tomato (Solanum lycopersicum) accumulates strictly acylsucroses, the South American wild relativeSolanum pennelliiproduces copious amounts of acylglucoses. Genetic, transgenic and biochemical dissection of theS. pennelliiacylglucose biosynthetic pathway identified a trichome gland cell expressed invertase-like enzyme that hydrolyzes acylsucroses (Sopen03g040490). This enzyme acts on the pyranose ring-acylated acylsucroses found in the wild tomato but not the furanose ring-decorated acylsucroses of cultivated tomato. These results show that modification of the core acylsucrose biosynthetic pathway leading to loss of furanose ring acylation set the stage for co-option of a general metabolic enzyme to produce a new class of protective compounds.
Molecular Evolution ofPseudomonas syringaeType III Secreted Effector Proteins
Authors: Dillon Marcus M. , Almeida Renan N.D. , Laflamme Bradley , Martel Alexandre , Weir Bevan S. , Desveaux Darrell , Guttman David S. 
Published: December 2018

ABSTRACTDiverse Gram-negative pathogens likePseudomonas syringaeemploy type III secreted effector (T3SE) proteins as primary virulence factors that combat host immunity and promote disease. T3SEs can also be recognized by plant hosts and activate an effector triggered immune (ETI) response that shifts the interaction back towards plant immunity. Consequently, T3SEs are pivotal in determining the virulence potential of individualP. syringaestrains, and ultimately restrictP. syringaepathogens to a subset of potential hosts that are unable to recognize their repertoires of T3SEs. While a number of effector families are known to be present in theP. syringaespecies complex, one of the most persistent challenges has been documenting the complex variation in T3SE contents across a diverse collection of strains. Using the entire pan-genome of 494P. syringaestrains isolated from more than 100 hosts, we conducted a global analysis of all known and putative T3SEs. We identified a total of 14,613 T3SEs, 4,636 of which were unique at the amino acid level, and show that T3SE repertoires of differentP. syringaestrains vary dramatically, even among strains isolated from the same hosts. We also find that dramatic diversification has occurred within many T3SE families, and in many cases find strong signatures of positive selection. Furthermore, we identify multiple gene gain and loss events for several families, demonstrating an important role of horizontal gene transfer (HGT) in the evolution ofP. syringaeT3SEs. These analyses provide insight into the evolutionary history ofP. syringaeT3SEs as they co-evolve with the host immune system, and dramatically expand the database ofP. syringaeT3SEs alleles.
A Historical, Detailed Toolmark Examination from 1916
Authors: Springer Eliot , Dumitra Aurora 
Published: December 2018

AbstractMarc Bischoff received his PhD from the University of Lausanne, Institute of Police Science and Criminology, and later became the head of the Institute. His final examination paper for his doctorate degree constitutes a toolmark analysis and comparison between a suspected axe and questioned cuttings of wood trunks. Bischoff uses the scientific method to test the hypothesis he formulated. Dated 1916, this report includes his notes, measurements, photomicrographs of the questioned toolmarks and the test impressions, detailed sketches, technical discussion, results, and conclusions. Recognizing the historical value of Bischoff's work, it seemed important to get it translated. Photocopies of Bischoff's original work were obtained. The case report, translated from French, is presented here along with a brief history of the Firearm and Toolmark Identification field and Bischoff's role in the beginning of this field. Bischoff's work stands as testimony to the long tradition of the field of forensic toolmark analysis.
Age estimation in a long‐lived seabird (Ardenna tenuirostris) using DNA methylation‐based biomarkers
Authors: De Paoli‐Iseppi Ricardo , Deagle Bruce E. , Polanowski Andrea M. , McMahon Clive R. , Dickinson Joanne L. , Hindell Mark A. , Jarman Simon N. 
Published: December 2018

AbstractAge structure is a fundamental aspect of animal population biology. Age is strongly related to individual physiological condition, reproductive potential and mortality rate. Currently, there are no robust molecular methods for age estimation in birds. Instead, individuals must be ringed as chicks to establish known‐age populations, which is a labour‐intensive and expensive process. The estimation of chronological age using DNA methylation (DNAm) is emerging as a robust approach in mammals including humans, mice and some non‐model species. Here, we quantified DNAm in whole blood samples from a total of 71 known‐age Short‐tailed shearwaters (Ardenna tenuirostris) using digital restriction enzyme analysis of methylation (DREAM). The DREAM method measures DNAm levels at thousands of CpG dinucleotides throughout the genome. We identified seven CpG sites with DNAm levels that correlated with age. A model based on these relationships estimated age with a mean difference of 2.8 years to known age, based on validation estimates from models created by repeated sampling of training and validation data subsets. Longitudinal observation of individuals re‐sampled over 1 or 2 years generally showed an increase in estimated age (6/7 cases). For the first time, we have shown that epigenetic changes with age can be detected in a wild bird. This approach should be of broad interest to researchers studying age biomarkers in non‐model species and will allow identification of markers that can be assessed using targeted techniques for accurate age estimation in large population studies.
Increased expression and altered subcellular distribution of cathepsin B in microglia induce cognitive impairment through oxidative stress and inflammatory response in mice
Authors: Ni Junjun , Wu Zhou , Stoka Veronika , Meng Jie , Hayashi Yoshinori , Peters Christoph , Qing Hong , Turk Vito , Nakanishi Hiroshi 
Published: December 2018

AbstractDuring normal aging, innate immunity progresses to a chronic state. However, how oxidative stress and chronic neuroinflammation arise during aging remains unclear. In this study, we found that genetic ablation of cathepsin B (CatB) in mice significantly reduced the generation of reactive oxygen species (ROS) and neuroinflammation and improved cognitive impairment during aging. In cultured microglia, pharmacological inhibition of CatB significantly reduced the generation of mitochondria‐derived ROS and proinflammatory mediators induced by L‐leucyl‐L‐leucine methyl ester (LLOMe), a lysosome‐destabilizing agent. In the CatB‐overexpressing microglia after treatment with LLOMe, which mimicked the aged microglia, CatB leaked in the cytosol is responsible for the degradation of the mitochondrial transcription factor A (TFAM), resulting in the increased generation of mitochondria‐derived ROS and proinflammatory mediators through impaired mtDNA biosynthesis. Furthermore, intralateral ventricle injection of LLOMe‐treated CatB‐overexpressing microglia induced cognitive impairment in middle‐aged mice. These results suggest that the increase and leakage of CatB in microglia during aging are responsible for the increased generation of mitochondria‐derived ROS and proinflammatory mediators, culminating in memory impairment.
The impact of vaping and regulatory environment on cigarette demand: behavioral economic perspective across four countries
Authors: Heckman Bryan W. , Fong Geoffrey T. , Borland Ron , Hitchman Sara , O’Connor Richard J. , Bickel Warren K. , Stein Jeffrey S. , Yong Hua‐Hie , Nahhas Georges J. , Pope Derek A. , Shang Ce , Cheng Kai‐Wen , Levy David T. , Cummings K. Michael 
Published: December 2018

AbstractBackground and AimsGovernment regulations of nicotine vaping products (NVP) have evolved rapidly during the past decade. The impact of NVP regulatory environment and vaping on cigarette demand is unknown. The current study aims to investigate whether or not respondents’ reported cigarette demand, as measured by a hypothetical cigarette purchase task, varies with (1) smoking status, (2) vaping status or (3) NVP regulatory environment (country used as proxy).DesignCross‐sectional survey data from wave 1 of the International Tobacco Control (ITC) Four Country Smoking and Vaping (4CV) Survey (2016).SettingAustralia, Canada, England and the United States.ParticipantsA total of 10 316 adult smokers.MeasurementsA hypothetical purchase task asked smokers to estimate how many cigarettes they would purchase for consumption in a single day across multiple cigarette prices. Responses were used to derive measures of cigarette demand. Overall sensitivity of cigarette consumption to price increases was quantified to index cigarette demand elasticity, whereas estimated consumption when cigarettes are free was used to index cigarette demand intensity.FindingsA majority of the non‐daily smokers had previously smoked daily (72.3%); daily vapers were more likely to be former daily smokers (89.9%) compared to non‐daily vapers (70.1%) and non‐vapers (69.2%) (P < 0.001). The smoking status × vaping status interaction was significant for cigarette demand intensity (F = 4.93; P = 0.007) and elasticity (F = 7.30; P = 0.001): among non‐daily smokers, vapers reported greater intensity but lower elasticity (i.e. greater demand) relative to non‐vapers (Ps < 0.05). Among daily smokers, daily vapers reported greater intensity relative to non‐vapers (P = 0.005), but vaping status did not impact elasticity (Ps > 0.38). Intensity was higher in Australia compared with all other countries (Ps < 0.001), but elasticity did not vary by country (F = 2.15; P = 0.09).ConclusionsIn a hypothetical purchase task, non‐daily smokers showed lower price elasticity if they used e‐cigarettes than if they did not, while there was no clear difference in elasticity between e‐cigarette users and non‐users among daily smokers or according to regulatory environment of their country with regard to e‐cigarettes.
Expressions of miR‐525‐3p and its target geneSEMG1in the spermatozoa of patients with asthenozoospermia
Authors: Zhou Q.‐z. , Guo X.‐b. , Zhang W.‐s. , Zhou J.‐h. , Yang C. , Bian J. , Chen M.‐k. , Guo W.‐b. , Wang P. , Qi T. , Wang C.‐y. , Yang J.‐k. , Liu C.‐d. 
Published: December 2018

AbstractBackgroundSemenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that theSEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear.ObjectivesTo study the molecular mechanism of high expression ofSEMG1 gene and its potential roles inAZS.Materials and MethodsWestern blot and real‐timePCRwere used to detect the expression levels ofSEMG1protein andmRNAin the ejaculated spermatozoa from normozoospermic males andAZSpatients. Bioinformatics analysis was used to predict miRNAs targeting forSEMG1 3′‐untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa inAZSpatients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind toSEMG1. Correlation of miR‐525‐3p andSEMG1mRNAexpression with clinical sperm parameters were also analyzed. Finally, we conducted a follow‐up study of reproductive history about all the subjects.ResultsSEMG1mRNAand protein level were significantly higher inAZSpatients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA‐525‐3p (miR‐525‐3p) which was predicted as a candidate regulator ofSEMG1was found lower expressed in ejaculatory spermatozoa inAZSpatients (p = 0.0074). Luciferase experiment revealed that microRNA‐525‐3p could directly targetSEMG13′‐untranslated region and suppress its expression. Importantly, our retrospective follow‐up study showed that both low miR‐525‐3p expression and highSEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility.Discussion and ConclusionThe elevated expression ofSEMG1 and reduced expression of miR‐525‐3p are associated withAZSand male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.
Maintenance rituximab or observation after frontline treatment with bendamustine‐rituximab for follicular lymphoma
Authors: Hill Brian T. , Nastoupil Loretta , Winter Allison M. , Becnel Melody R. , Cerhan James R. , Habermann Thomas M. , Link Brian K. , Maurer Matthew J. , Fakhri Bita , Reddy Prathima , Smith Stephen D. , Mukhija Dhruvika , Jagadeesh Deepa , Desai Amrita , Alderuccio Juan Pablo , Lossos Izidore S. , Mehra Pooja , Portell Craig A. , Goldman Max L. , Calzada Oscar , Cohen Jonathon B. , Hussain Mohammad J. , Ghosh Nilanjan , Caimi Paolo , Tiutan Timothy , Martin Peter , Kodali Abhigna , Evens Andrew M. , Kahl Brad S. 
Published: December 2018

SummaryBendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R‐CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.
Neural correlates of cue‐ and stress‐induced craving in gambling disorders: implications for transcranial magnetic stimulation interventions
Authors: Spagnolo Primavera A. , Gómez Pérez Luis J. , Terraneo Alberto , Gallimberti Luigi , Bonci Antonello 
Published: December 2018

AbstractGambling disorder (GD), currently considered a behavioral addiction, shows substantial similarities with substance use disorders (SUDs) in terms of neurobiology and phenomenology. These similarities have been recognized in the DSM‐5, although several relevant differences still exist in the diagnostic criteria, in particular, with regard to the role of cue‐ and stress‐ induced craving. Craving, recently included as a new criterion for SUDs diagnosis only, is a key construct also in the pathophysiology of GD. Furthermore, brain imaging studies indicate that similar alterations in cortico‐limbic‐striatal and prefrontal control circuits underlie the emergence of craving states in both disorders. This has important implications for the identification of neurobiologically based anti‐craving interventions, which may be used for both GD and SUDs. In this regard, a novel neuromodulation intervention, named repetitive transcranial magnetic stimulation (rTMS), is emerging as a promising treatment for craving in SUDs, and could potentially be effective also in treating gambling urges. Here, we review the clinical neurobiological research on GD, with a specific emphasis on the neural circuits implicated in cue‐ and stress‐craving, taking SUDs as the major comparative example. Furthermore, we describe the studies that have evaluated rTMS as a therapeutic tool for targeting and restoring the neural alterations underlying gambling urge. The manuscript concludes discussing some of the limitations of the current studies, and suggests directions for future rTMS research in GD.