bluuebunny/crossref_metadata_2025_split huggingface dataset:
fISHing with immunohistochemistry for housekeeping gene changes in Alzheimer’s disease using an automated quantitative analysis workflow
Authors: Highet Blake , Vikas Anekal Praju , Ryan Brigid , Murray Helen , Coppieters Natacha , Victor Dieriks Birger , Singh‐Bains Malvindar K. , Mehrabi Nasim F. , Faull Richard L. M. , Dragunow Michael , Curtis Maurice A. 
Published: December 2020

AbstractIn situ hybridization (ISH) is a powerful tool that can be used to localize mRNA expression in tissue samples. Combining ISH with immunohistochemistry (IHC) to determine cell type provides cellular context of mRNA expression, which cannot be achieved with gene microarray or polymerase chain reaction. To study mRNA and protein expression on the same section we investigated the use of RNAscope® ISH in combination with fluorescent IHC on paraffin‐embedded human brain tissue. We first developed a high‐throughput, automated image analysis workflow for quantifying RNA puncta across the total cell population and within neurons identified by NeuN+ immunoreactivity. We then applied this automated analysis to tissue microarray (TMA) sections of middle temporal gyrus tissue (MTG) from neurologically normal and Alzheimer's Disease (AD) cases to determine the suitability of three commonly used housekeeping genes: ubiquitin C (UBC), peptidyl‐prolyl cis‐trans isomerase B (PPIB) and DNA‐directed RNA polymerase II subunit RPB1 (POLR2A). Overall, we saw a significant decrease in total and neuronal UBC expression in AD cases compared to normal cases. Total expression results were validated with RT‐qPCR using fresh frozen tissue from 5 normal and 5 AD cases. We conclude that this technique combined with our novel automated analysis pipeline provides a suitable platform to study changes in gene expression in diseased human brain tissue with cellular and anatomical context. Furthermore, our results suggest that UBC is not a suitable housekeeping gene in the study of post‐mortem AD brain tissue.
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Microbiota‐gut‐brain axis as a regulator of reward processes
Authors: García‐Cabrerizo Rubén , Carbia Carina , O´Riordan Kenneth J. , Schellekens Harriet , Cryan John F. 
Published: December 2020

AbstractOur gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e. eating, social or sexual behaviours) and non‐natural reinforcers (drug addiction behaviours including those relevant to alcohol, psychostimulants, opioids and cannabinoids). We will integrate preclinical and clinical evidence suggesting that the microbiota‐gut‐brain axis could be implicated in the development of disorders associated with alterations in the reward system and how it may be targeted as a promising therapeutic strategy.
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Cover Image for this issue: https://doi.org/10.1111/jnc.15065.
An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease
Authors: Best Hannah L. , Clare Alison J. , McDonald Kirstin O. , Wicky Hollie E. , Hughes Stephanie M. 
Published: December 2020

AbstractNeuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders. In addition to the accumulation of auto‐fluorescent storage material in lysosomes, NCLs are largely characterised by region‐specific neuroinflammation that can predict neuron loss. These phenotypes suggest alterations in the extracellular environment—making the secretome an area of significant interest. This study investigated the secretome in the CLN6 (ceroid‐lipofuscinosis neuronal protein 6) variant of NCL. To investigate the CLN6 secretome, we co‐cultured neurons and glia isolated from Cln6nclf or Cln6± mice, and utilised mass spectrometry to compare protein constituents of conditioned media. The significant changes noted in cathepsin enzymes, were investigated further via western blotting and enzyme activity assays. Viral‐mediated gene therapy was used to try and rescue the wild‐type phenotype and restore the secretome—both in vitro in co‐cultures and in vivo in mouse plasma. In Cln6nclf cells, proteomics revealed a marked increase in catabolic and cytoskeletal‐associated proteins—revealing new similarities between the pathogenic signatures of NCLs with other neurodegenerative disorders. These changes were, in part, corrected by gene therapy intervention, suggesting these proteins as candidate in vitro biomarkers. Importantly, these in vitro changes show promise for in vivo translation, with Cathepsin L (CTSL) activity reduced in both co‐cultures and Cln6nclf plasma samples post gene‐therapy. This work suggests the secretome plays a role in CLN6 pathogenesis and highlights its potential use as an in vitro model. Proteomic changes present a list of candidate biomarkers for monitoring disease and assessing potential therapeutics in future studies.
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Multimodal MRI Response to Fingolimod in Multiple Sclerosis: A Nonrandomized, Single Arm, Observational Study
Authors: Bernitsas Evanthia , Kopinsky Hannah , Lichtman‐Mikol Samuel , Razmjou Sarah , Santiago‐Martinez Carla , Yarraguntla Kalyan , Bao Fen 
Published: December 2020

ABSTRACTBACKGROUND AND PURPOSEFingolimod has a favorable effect on conventional MRI measures; however, its neuroprotective effect is not clear. We aim to investigate changes of conventional and advanced MRI measures in lesions and normal‐appearing white matter (NAWM) over 2 years in fingolimod‐treated patients.METHODSFifty relapsing‐remitting multiple sclerosis patients and 27 healthy controls were enrolled in the study and underwent baseline, 1‐year, and 2‐year 3T MRI scans. T2 lesion volume, whole brain volume, cortical gray matter volume, white matter volume, corpus callosum area, percentage brain volume change (PBVC), Expanded Disability Status Scale, gadolinium‐enhancing lesions, PBVC, magnetization transfer ratio (MTR), and diffusion tensor imaging metrics (fractional anisotropy [FA] and median diffusivity [MD]) in lesions and NAWM were calculated. Longitudinal changes were examined using one‐way repeated measures ANOVA. Bonferroni correction for multiple testing was used when appropriate.RESULTSConventional MRI measures were unchanged in both groups. Lesion MTR increased significantly (P < .001), but NAWM‐MTR remained unchanged. Lesion FA improved significantly in year 1 (P = .003) and over the study duration (P = .05). Lesion MD changed significantly from baseline to year 1 (P < .001) and remained stable over 2 years. NAWM‐FA was significant from baseline to year 1 (P = .002) and from baseline to year 2 (P < .001). NAWM‐MD was significant only from baseline to year 1 (P = .001).CONCLUSIONSThese findings suggest a possible neuroreparative effect of fingolimod on the MS lesions and NAWM. Larger and longer randomized studies are required to confirm these results.
Imaging Transcriptomics in Neurodegenerative Diseases
Authors: Mroczek Magdalena , Desouky Ahmed , Sirry Wadid 
Published: December 2020

ABSTRACTImaging transcriptomics investigates the relationship between neuroanatomical/neuroimaging features and gene expression. The spatial and temporal distribution of the expressed genes and their pattern of spreading over time can contribute to elucidating cellular and molecular processes involved in neurodegeneration. In this study, we review recent findings regarding the correlation between neuroimaging and expression data in neurodegenerative diseases with a focus on Alzheimer's disease and Parkinson's disease. An association between gene expression data and different neuroimaging neurodegeneration features, such as R2 relaxation time and volumetric cortical atrophy, was established. Several positive and negative expression correlations were identified, and they confirmed the focal nature of neurodegeneration. Positively correlated genes were associated with cell motility, immune system activity, neuroinflammation, and microglia. Data from connectome studies support the hypothesis of selective network vulnerability and a temporal spreading pattern in neurodegenerative pathologies. Genes related to cellular mobility and transport are overexpressed in the neuroimaging‐defined delineated areas of degeneration. In addition, expression enrichment of genes involved in immunological processes in vulnerable regions—such as the Toll‐like receptor, a receptor involved in innate immunity—plays a major role in neuroinflammation in neurodegenerative diseases. However, substantial limitations must be overcome in future studies: the lack of high‐quality resolution expression data, the lack of standardized study protocols, and insufficient sensitive early stage neuroimaging markers of degeneration. Identifying neuroimaging and expression prodromal biomarkers and investigating their causal relation in the preclinical disease stage may enable early targeted therapy before the onset of irreversible brain changes.
Association between TNF‐α G‐308A (rs1800629) polymorphism and susceptibility to chronic periodontitis and type 2 diabetes mellitus: A meta‐analysis
Authors: Shi Liu‐Xia , Zhang Liu , Zhang Dong‐Lin , Zhou Jing‐Ping , Jiang Xue‐Juan , Jin Yue‐Long , Chang Wei‐Wei 
Published: December 2020

AbstractBackground and objectiveAlthough the association between tumor necrosis factor‐α (TNF‐α) G‐308A (rs1800629) polymorphism and chronic periodontitis (CP), chronic periodontitis with type 2 diabetes mellitus (DP) is assumed, results of this association have been contradictory. The aim of this study was to assess the relationship between rs1800629 polymorphism and CP/DP susceptibility.MethodsWe searched for studies on PubMed, Web of Science, MEDLINE, Chinese National Infrastructure, and WanFang databases. Study selection was performed using specific inclusion and exclusion criteria and fulfilled the PECO (participant, exposure, comparison, and outcome) format. The relationship between rs1800629 polymorphism and CP/DP susceptibility was evaluated by the effect summary odds ratio (OR) and 95% confidence intervals (CIs). Allele, dominant, and recessive genetic models were computed to assess the strength of the association.ResultsA total of 25 case‐control studies were included in the analysis. In the Asian population, TNF‐α rs1800629 polymorphism was found to be significantly associated with CP in the overall analyses and for all genetic contrasts, while no significant risks were found among Caucasian populations for all genetic contrasts. The TNF‐α rs1800629 polymorphism was also associated with increased DP risk in Asians under the fixed‐effects model, but not in the recessive comparison.ConclusionThe meta‐analysis suggested that TNF‐α rs1800629 polymorphism might affect the risk of CP and DP, particularly in individuals of Asian descent.
Oral microbiota and atherothrombotic carotid plaque vulnerability in periodontitis patients. A cross‐sectional study
Authors: Brun Adrian , Nuzzo Alexandre , Prouvost Bastien , Diallo Devy , Hamdan Sandrella , Meseguer Elena , Guidoux Céline , Lavallée Philippa , Amarenco Pierre , Lesèche Guy , Bouchard Philippe , Michel Jean‐Baptiste , Rangé Hélène 
Published: December 2020

AbstractBackgroundAn increased risk of atherothrombotic vascular events has been reported in periodontitis patients. Periodontitis is associated with dysbiotic subgingival biofilms and bacteremia.ObjectiveWe hypothesized (a) that the oral microbiome is associated with the carotid microbiome and (b) that periodontitis could contribute to plaque vulnerability. The aim of this study was to determine the associations between periodontitis, the carotid microbiome, and the local innate immune response in carotid atherothrombotic plaques vulnerable to rupture.MethodsIn this cross‐sectional study, 45 patients admitted for carotid endarterectomy underwent a preoperative periodontal examination. The volume of intraplaque hemorrhage reflected by the hemoglobin level released in carotid‐conditioned media was considered as a criterion of carotid plaque vulnerability. Levels of antibodies against periodontal bacteria were determined in sera. The signature of the oral microbiota was assessed by microbial whole‐genome sequencing, nested PCR, and immunostaining in carotid plaque samples. Markers of neutrophil recruitment (leukotriene B4), neutrophil activation (myeloperoxidase, defensins), and cytokines were measured in carotid‐conditioned media and/or plasma.ResultsAll patients exhibited periodontitis. One hundred and forty‐four bacterial genera were detected in the carotid microbiome. WhileStreptococcuswas found in 84% of the carotid samples, periodontitis‐associated genera were detected in 21%.P. gingivalisDNA and gingipains were also identified in carotid samples. There were significant inverse correlations between periodontal attachment loss/serum anti‐P. gingivalisImmunoglobulin A and cytokine inhibiting neutrophils (allP < .01). There were also significant positive correlations between lipopolysaccharides, myeloperoxidase/human neutrophil peptides1‐3, and hemoglobin levels (allP < .01).ConclusionsIn patients at risk of stroke, the carotid plaque microbiome was highly diverse and compatible with an oral origin. Periodontitis was significantly associated with neutrophil activation markers and plaque vulnerability to rupture.
A framework infrageneric classification ofCarex(Cyperaceae) and its organizing principles
Authors:   Global Carex Group, Roalson Eric H. , Jiménez‐Mejías Pedro , Hipp Andrew L. , Benítez‐Benítez Carmen , Bruederle Leo P. , Chung Kyong‐Sook , Escudero Marcial , Ford Bruce A. , Ford Kerry , Gebauer Sebastian , Gehrke Berit , Hahn Marlene , Hayat Muhammad Qasim , Hoffmann Mathias H. , Jin Xiao‐Feng , Kim Sangtae , Larridon Isabel , Léveillé‐Bourret Étienne , Lu Yi‐Fei , Luceño Modesto , Maguilla Enrique , Márquez‐Corro Jose Ignacio , Martín‐Bravo Santiago , Masaki Tomomi , Míguez Mónica , Naczi Robert F. C. , Reznicek Anton A. , Spalink Daniel , Starr Julian R. , Uzma  , Villaverde Tamara , Waterway Marcia J. , Wilson Karen L. , Zhang Shu‐Ren 
Published: December 2020

AbstractPhylogenetic studies ofCarexL. (Cyperaceae) have consistently demonstrated that most subgenera and sections are para‐ or polyphyletic. Yet, taxonomists continue to use subgenera and sections inCarexclassification. Why? The GlobalCarexGroup (GCG) here takes the position that the historical and continued use of subgenera and sections serves to (i) organize our understanding of lineages inCarex, (ii) create an identification mechanism to break the ~2000 species ofCarexinto manageable groups and stimulate its study, and (iii) provide a framework to recognize morphologically diagnosable lineages withinCarex. Unfortunately, the current understanding of phylogenetic relationships inCarexis not yet sufficient for a global reclassification of the genus within a Linnean infrageneric (sectional) framework. Rather than leavingCarexclassification in its current state, which is misleading and confusing, we here take the intermediate steps of implementing the recently revised subgeneric classification and using a combination of informally named clades and formally named sections to reflect the current state of our knowledge. This hybrid classification framework is presented in an order corresponding to a linear arrangement of the clades on a ladderized phylogeny, largely based on the recent phylogenies published by the GCG. It organizesCarexinto six subgenera, which are, in turn, subdivided into 62 formally named Linnean sections plus 49 informal groups. This framework will serve as a roadmap for research onCarexphylogeny, enabling further development of a complete reclassification by presenting relevant morphological and geographical information on clades where possible and standardizing the use of formal sectional names.
Economic effects of predation by scaup on baitfish and sportfish farms
Authors: Engle Carole R. , Clements Stephen , Dorr Brian S. , Davis J. Brian , Roy Luke A. , Kelly Anita M. 
Published: December 2020

AbstractFish‐eating birds have been found to consume baitfish and sportfish raised on farms in the United States. Understanding the on‐farm economic effects of such wildlife conflicts is essential for wildlife management agencies to make informed decisions. Lesser scaup, while not widely considered a fish‐eating bird, will consume farmed fish. Baitfish and sportfish farms in Arkansas (the major baitfish and sportfish producing‐state in the U.S.) were surveyed to gather data on the cost of protecting farm crops from scaup. The values of lost sales revenue from the various species of baitfish and sportfish consumed by scaup were estimated based on a concomitant field study on the abundance, distribution, and dietary habits of scaup that visited Arkansas baitfish and sportfish farms during winters of 2016–2017 and 2017–2018. Economic effects were estimated for golden shiner, fathead minnow, sportfish, and goldfish farms. Total annual costs to scare birds from baitfish and sportfish farms were $622 ± 742 per ha. The greatest components of bird‐scaring costs were manpower (56%), truck usage (32%), levee upkeep for vehicle access to scare birds (9%), firearms and ammunition (2%), and pyrotechnic devices (1%). The combined annual economic losses, calculated as reduced revenue from fish losses to scaup plus expenditures to scare birds, averaged $683/ha for golden shiners, $695/ha for fathead minnows, $663/ha for sportfish, and $673/ha for goldfish across the two study years. The fish losses to scaup alone averaged $1.06 million per year ($0.09 million in Year 1 and $2.03 million in Year 2) for the Arkansas baitfish industry. Total direct negative economic effects on the Arkansas baitfish industry were estimated to be, on average, $5.5 million per year ($4.6 in Year 1 and $6.3 million in Year 2).
The Gubernacular Canal…
Authors: Radia Ria , Loughlin Amanda , Makdissi Jimmy 
Published: December 2020

AbstractThe Gubernacular Canal is an anatomical structure that can be seen on Cone Beam Computed Tomography, connecting the dental lamina of an unerupted tooth the overlying gingivae at the site of normal eruption. We present the case of a transposed canine with an associated Gubernacular Canal seen on CBCT. With the use of CBCT becoming more prevalent, we would like to highlight the presence and significance of this structure, as clinicians are likely to encounter it on CBCT.
Epidural versus general anesthesia for open pyloromyotomy in infants: A retrospective observational study
Authors: Opfermann Philipp , Wiener Caspar , Schmid Werner , Zadrazil Markus , Metzelder Martin , Kimberger Oliver , Marhofer Peter 
Published: December 2020

AbstractBackgroundThoracic epidural anesthesia for open infantile hypertrophic pyloric stenosis surgery is a controversial issue in the presence of little comparative data.AimsTo compare this approach to general anesthesia for desaturation events (≤90% oxygen saturation) and absolute values of minimal oxygen saturation, minimal heart frequency, operating‐room occupancy time, and durations of surgery in a retrospective study design.MethodsData were retrieved for patients with infantile hypertrophic pyloric stenosis managed by thoracic epidurals under sedation or general anesthesia with rapid sequence induction between 01/2007 and 12/2017. Oxygen saturation and heart rate were analyzed over eight 5‐minutes intervals relative to the start of anesthesia / sedation (four‐time intervals) and before discharge of the patient from the operating room (four‐time intervals). Fisher's exact tests and mixed model two‐way analysis of variance for repeated measures were employed for intergroup comparisons.ResultsThe epidural and general anesthesia groups included 69 and 32 evaluable infants, respectively. Patients managed under epidural anesthesia had cumulatively higher minimimal mean (SD) oxygen saturation values (98.2 [2.6] % versus 96.6 [5.2] %, p < 0.001) and lower minimal mean (SD) heart rate values (127.9 [15.0] beats per minute versus 140.7 [17.2] beats per minute, p < 0.001) over time. Similarly, the frequency of desaturation events (defined as ≤90% oxygen saturation) was significantly lower for these patients during the period of 5 minutes after induction of sedation or general anesthesia (odds ratio 7.4 [2.1–25.9]; p = 0.001) and during the subsequent period of five minutes (odds ratio 6.2 [1.1–33.9]; p = 0.031). One case of prolonged respiratory weaning was observed in the general anesthesia group. The mean (SD) operating‐room occupancy was 61.9 (16.6) minutes for the epidural anesthesia group versus 73.3 (22.2) minutes for the general anesthesia group (p = 0.005) as a result of shorter emergence from sedation.ConclusionsIn our series, maintaining spontaneous breathing with minimal airway manipulation in patients undergoing open repair of hypertrophic pyloric stenosis under single‐shot epidural anesthesia resulted in fewer desaturation events ≤90% than general anesthesia. In addition, this approach seems to result in shorter turnover times in the operating room.
Natural variation in the promoter of GsERD15B affects salt tolerance in soybean
Authors: Jin Ting , Sun Yangyang , Shan Zhong , He Jianbo , Wang Ning , Gai Junyi , Li Yan 
Published: December 2020

SummarySalt stress has detrimental effects on crop growth and yield, and the area of salt‐affected land is increasing. Soybean is a major source of vegetable protein, oil and feed, but considered as a salt‐sensitive crop. Cultivated soybean (Glycine max) is domesticated from wild soybean (G. soja) but lost considerable amount of genetic diversity during the artificial selection. Therefore, it is important to exploit the gene pool of wild soybean. In this study, we identified 34 salt‐tolerant accessions from wild soybean germplasm and found that a 7‐bp insertion/deletion (InDel) in the promoter of GsERD15B (early responsive to dehydration 15B) significantly affects the salt tolerance of soybean. GsERD15B encodes a protein with transcriptional activation function and contains a PAM2 domain to mediate its interaction with poly(A)‐binding (PAB) proteins. The 7‐bp deletion in GsERD15B promoter enhanced the salt tolerance of soybean, with increased up‐regulation of GsERD15B, two GmPAB genes, the known stress‐related genes including GmABI1, GmABI2, GmbZIP1, GmP5CS, GmCAT4, GmPIP1:6, GmMYB84 and GmSOS1 in response to salt stress. We propose that natural variation in GsERD15B promoter affects soybean salt tolerance, and overexpression of GsERD15B enhanced salt tolerance probably by increasing the expression levels of genes related to ABA‐signalling, proline content, catalase peroxidase, dehydration response and cation transport.