bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term consumption of caffeine-free high sucrose cola beverages aggravates the pathogenesis of EAE in mice
Authors: Cao Guangchao , Wang Qian , Huang Wanjun , Tong Jiyu , Ye Dewei , He Yan , Liu Zonghua , Tang Xin , Cheng Hao , Wen Qiong , Li Dehai , Chau Hau-Tak , Wen Yiming , Zhong Hui , Meng Ziyu , Liu Hui , Wu Zhenzhou , Zhao Liqing , Flavell Richard A , Zhou Hongwei , Xu Aimin , Yang Hengwen , Yin Zhinan 
Published: June 2017

AbstractEpidemiological data provide strong evidence of dramatically increasing incidences of many autoimmune diseases in the past few decades, mainly in western and westernized countries. Recent studies clearly revealed that ‘Western diet’ increases the risk of autoimmune diseases at least partially via disrupting intestinal tight junctions and altering the construction and metabolites of microbiota. However, the role of high sucrose cola beverages (HSCBs), which are one of the main sources of added sugar in the western diet, is barely known. Recently, a population study showed that regular consumption of sugar-sweetened beverages is associated with increased risk of seropositive rheumatoid arthritis in women, which provokes interest in the genuine effects of these beverages on the pathogenesis of autoimmune diseases and the underlying mechanisms. Here we showed that long-term consumption of caffeine-free HSCBs aggravated the pathogenesis of experimental autoimmune encephalomyelitis in mice in a microbiota-dependent manner. Further investigation revealed that HSCBs altered community structure of microbiota and increased Th17 cells. High sucrose consumption had similar detrimental effects while caffeine contamination limited the infiltrated pathogenic immune cells and counteracted these effects. These results uncovered a deleterious role of decaffeinated HSCBs in aggravating the pathogenesis of experimental autoimmune encephalomyelitis in mice.
Bioengineered constructs combined with exercise enhance stem cell-mediated treatment of volumetric muscle loss
Authors: Quarta Marco , Cromie Melinda , Chacon Robert , Blonigan Justin , Garcia Victor , Akimenko Igor , Hamer Mark , Paine Patrick , Stok Merel , Shrager Joseph B. , Rando Thomas A. 
Published: June 2017

AbstractVolumetric muscle loss (VML) is associated with loss of skeletal muscle function, and current treatments show limited efficacy. Here we show that bioconstructs suffused with genetically-labelled muscle stem cells (MuSCs) and other muscle resident cells (MRCs) are effective to treat VML injuries in mice. Imaging of bioconstructs implanted in damaged muscles indicates MuSCs survival and growth, and ex vivo analyses show force restoration of treated muscles. Histological analysis highlights myofibre formation, neovascularisation, but insufficient innervation. Both innervation and in vivo force production are enhanced when implantation of bioconstructs is followed by an exercise regimen. Significant improvements are also observed when bioconstructs are used to treat chronic VML injury models. Finally, we demonstrate that bioconstructs made with human MuSCs and MRCs can generate functional muscle tissue in our VML model. These data suggest that stem cell-based therapies aimed to engineer tissue in vivo may be effective to treat acute and chronic VML.
Construction of a synthetic metabolic pathway for biosynthesis of the non-natural methionine precursor 2,4-dihydroxybutyric acid
Authors: Walther Thomas , Topham Christopher M. , Irague Romain , Auriol Clément , Baylac Audrey , Cordier Hélène , Dressaire Clémentine , Lozano-Huguet Luce , Tarrat Nathalie , Martineau Nelly , Stodel Marion , Malbert Yannick , Maestracci Marc , Huet Robert , André Isabelle , Remaud-Siméon Magali , François Jean Marie 
Published: June 2017

Abstract2,4-Dihydroxybutyric acid (DHB) is a molecule with considerable potential as a versatile chemical synthon. Notably, it may serve as a precursor for chemical synthesis of the methionine analogue 2-hydroxy-4-(methylthio)butyrate, thus, targeting a considerable market in animal nutrition. However, no natural metabolic pathway exists for the biosynthesis of DHB. Here we have therefore conceived a three-step metabolic pathway for the synthesis of DHB starting from the natural metabolite malate. The pathway employs previously unreported malate kinase, malate semialdehyde dehydrogenase and malate semialdehyde reductase activities. The kinase and semialdehyde dehydrogenase activities were obtained by rational design based on structural and mechanistic knowledge of candidate enzymes acting on sterically cognate substrates. Malate semialdehyde reductase activity was identified from an initial screening of several natural enzymes, and was further improved by rational design. The pathway was expressed in a minimally engineered Escherichia coli strain and produces 1.8 g l−1 DHB with a molar yield of 0.15.
Imaging tau pathology in Parkinsonisms
Authors: Coakeley Sarah , Strafella Antonio P. 
Published: June 2017

AbstractThe recent development of positron emission tomography radiotracers targeting pathological tau in vivo has led to numerous human trials. While investigations have primarily focused on the most common tauopathy, Alzheimer’s disease, it is imperative that testing also be performed in parkinsonian tauopathies, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregates differ in isoforms and conformations across disorders, and as a result one radiotracer may not be appropriate for all tauopathies. In this review, we evaluate the preclinical and clinical reports of current tau radiotracers in parkinsonian disorders. These radiotracers include [18F]FDDNP, [11C]PBB3, [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 ([18F]T807). There are concerns of off-target binding with [18F]FDDNP and [11C]PBB3, which may increase the signal to noise ratio and thereby decrease the efficacy of these radiotracers. Testing in [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 has been performed in progressive supranuclear palsy, while [18F]THK-5317 and [18F]AV-1451 have also been tested in corticobasal degeneration patients. [18F]THK-5317 and [18F]THK-5351 have demonstrated binding in brain regions known to be afflicted with pathological tau; however, due to small sample sizes these studies should be replicated before concluding their appropriateness in parkinsonian tauopathies. [18F]AV-1451 has demonstrated mixed results in progressive supranuclear palsy patients and post-mortem analysis shows minimal to no binding to non-Alzheimer’s disease tauopathies brain slices.
Testing hypotheses of developmental constraints on mammalian brain partition evolution, using marsupials
Authors: Carlisle Alison , Selwood Lynne , Hinds Lyn A. , Saunders Norman , Habgood Mark , Mardon Karine , Weisbecker Vera 
Published: June 2017

AbstractThere is considerable debate about whether the partition volumes of the mammalian brain (e.g. cerebrum, cerebellum) evolve according to functional selection, or whether developmental constraints of conserved neurogenetic scheduling cause predictable partition scaling with brain size. Here we provide the first investigation of developmental constraints on partition volume growth, derived from contrast-enhanced micro-computed tomography of hydrogel-stabilized brains from three marsupial species. ANCOVAs of partition vs. brain volume scaling, as well as growth curve comparisons, do not support several hypotheses consistent with developmental constraints: brain partition growth significantly differs between species, or between developing vs. adult marsupials. Partition growth appears independent of adult brain volume, with no discernable growth spurts/lags relatable to internal structural change. Rather, adult proportion differences appear to arise through growth rate/duration heterochrony. Substantial phylogenetic signal in adult brain partitions scaling with brain volume also counters expectations of development-mediated partition scaling conservatism. However, the scaling of olfactory bulb growth is markedly irregular, consistent with suggestions that it is less constrained. The very regular partition growth curves suggest intraspecific developmental rigidity. We speculate that a rigid, possibly neuromer-model-like early molecular program might be responsible both for regular growth curves within species and impressions of a link between neurogenesis and partition evolution.
The prognostic significance of PD-L1 expression in patients with glioma: A meta-analysis
Authors: Xue Song , Song Ge , Yu Jinming 
Published: June 2017

AbstractA large number of studies have shown that programmed death-ligand 1 (PD-L1) is abnormally expressed in gliomas. However, the prognostic significance of PD-L1 expression in glioma patients remains unresolved. Accordingly, we conducted a meta-analysis to determine the prognostic role of high PD-L1 in patients with glioma. Electronic databases were searched to identify studies evaluating PD-L1 expression and overall survival (OS) in these patients. A total of 6 studies (published in 4 articles) that involved 1052 patients were included. Pooled results showed that high PD-L1 expression was associated with worse OS in glioma patients (HR = 1.30, 95% CI: 1.02–1.65, P = 0.032). Further subgroup analysis indicated that high PD-L1 expression in glioblastoma (GBM) was also associated with worse OS (HR = 1.40, 95% CI: 1.03–1.90, P = 0.030). Conversely, in index subgroup analysis, neither PD-L1 protein (HR = 1.43, 95% CI: 0.97–2.10, P = 0.068) nor gene (HR = 1.20, 95% CI: 0.83–1.74, P = 0.322) expression was significantly associated with OS. PD-L1 may represent a promising biomarker that predicts disease progression in patients with glioma or GBM. However, because of our limited sample size, further prospective or retrospective multi-centre, well-designed studies should be performed to verify this result.
Human in vitro-induced regulatory T cells display Dlgh1 dependent and PKC-θ restrained suppressive activity
Authors: Zanin-Zhorov Alexandra , Kumari Sudha , Hippen Keli L. , Merkel Sarah C. , MacMillan Margaret L. , Blazar Bruce R. , Dustin Michael L. 
Published: June 2017

AbstractIn vitro induced human regulatory T cells (iTregs) have demonstrated in vivo therapeutic utility, but pathways regulating their function have not been elucidated. Here, we report that human iTregs generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C (PKC)-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. Also, iTregs display elevated Dlgh1 overall and Dlgh1-dependent p38 phosphorylation, higher levels of phosphatase and tensin homolog (PTEN), and diminished Akt phosphorylation. Pharmacological interruption of PKC-θ increases and Dlgh1 silencing decreases the ability of iTregs to suppress interferon-γ production by CD4+CD25− effector T cells (Teff). Comparison with expanded cord blood-derived CD4+CD25hi tTreg and expanded Teffs from the same donors indicate that iTreg are intermediate between expanded CD4+CD25hi tTregs and Teffs, whereas modulation of suppressive activities by PKC-θ and Dlgh1 signaling pathways are shared.
Congenital deafness is associated with specific somatosensory deficits in adolescents
Authors: Moshourab Rabih , Bégay Valérie , Wetzel Christiane , Walcher Jan , Middleton Steven , Gross Manfred , Lewin Gary R. 
Published: June 2017

AbstractHearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. Here we used a battery of quantitative sensory tests to probe touch, thermal and pain sensitivity in a young control population (14–20 years old) compared to age-matched individuals with congenital hearing loss. Sensory testing was performed on the dominant hand of 111 individuals with normal hearing and 36 with congenital hearing loss. Subjects with congenital deafness were characterized by significantly higher vibration detection thresholds at 10 Hz (2-fold increase, P < 0.001) and 125 Hz (P < 0.05) compared to controls. These sensory changes were not accompanied by any major change in measures of pain perception. We also observed a highly significant reduction (30% compared to controls p < 0.001) in the ability of hearing impaired individual’s ability to detect cooling which was not accompanied by changes in warm detection. At least 60% of children with non-syndromic hearing loss showed very significant loss of vibration detection ability (at 10 Hz) compared to age-matched controls. We thus propose that many pathogenic mutations that cause childhood onset deafness may also play a role in the development or functional maintenance of somatic mechanoreceptors.
Altered brain metabolic connectivity at multiscale level in early Parkinson’s disease
Authors: Sala Arianna , Caminiti Silvia Paola , Presotto Luca , Premi Enrico , Pilotto Andrea , Turrone Rosanna , Cosseddu Maura , Alberici Antonella , Paghera Barbara , Borroni Barbara , Padovani Alessandro , Perani Daniela 
Published: June 2017

AbstractTo explore the effects of PD pathology on brain connectivity, we characterized with an emergent computational approach the brain metabolic connectome using [18F]FDG-PET in early idiopathic PD patients. We applied whole-brain and pathology-based connectivity analyses, using sparse-inverse covariance estimation in thirty-four cognitively normal PD cases and thirty-four age-matched healthy subjects for comparisons. Further, we assessed high-order resting state networks by interregional correlation analysis. Whole-brain analysis revealed altered metabolic connectivity in PD, with local decreases in frontolateral cortex and cerebellum and increases in the basal ganglia. Widespread long-distance decreases were present within the frontolateral cortex as opposed to connectivity increases in posterior cortical regions, all suggestive of a global-scale connectivity reconfiguration. The pathology-based analyses revealed significant connectivity impairment in the nigrostriatal dopaminergic pathway and in the regions early affected by α-synuclein pathology. Notably, significant connectivity changes were present in several resting state networks especially in frontal regions. These findings expand previous imaging evidence of altered connectivity in cognitively stable PD patients by showing pathology-based connectivity changes and disease-specific metabolic architecture reconfiguration at multiple scale levels, from the earliest PD phases. These alterations go well beyond the known striato-cortical connectivity derangement supporting in vivo an extended neural vulnerability in the PD synucleinopathy.
Effects of Epigallocatechin-3-gallate (EGCG) on the bond strength of fiber posts to Sodium hypochlorite (NaOCl) treated intraradicular dentin
Authors: Yu Hao-han , Zhang Ling , Xu Shuai , Li Fang , Yu Fan , Liu Zheng-ya , Huang Li , Chen Ji-hua 
Published: June 2017

AbstractThis study was to evaluate the effect of Epigallocatechin-3-gallate (EGCG) on the bond strength of two adhesive systems to the Sodium hypochlorite (NaOCl) treated intraradicular dentin. The roots were accepted regular root canal treatments and post space preparations, and further divided into eight groups according to the four post space pretreatments and two dentin adhesives [Single Bond 2 (SB2) and Clearfil SE Bond (CSB)] used. The push-out strength before and after thermocycling in different root region (coronal and apical), DC of the adhesive and morphologic patterns of treated post space were evaluated. NaOCl + EGCG groups showed the highest push-out strength regardless of the adhesive type, root region and time (P < 0.05). NaOCl pretreatment significantly decreased the push-out strengths and DC of CSB (P < 0.05). EGCG could improve the bonding properties of both SB2 and CSB to NaOCl treated intraradicular dentin. The effect of NaOCl on bonding of a fiber post depended on the type of the adhesive.
Serum hepcidin may be a novel uremic toxin, which might be related to erythropoietin resistance
Authors: Lee Sung Woo , Kim Jeong Min , Lim Hye Jin , Hwang Young-Hwan , Kim Soo Wan , Chung Wookyung , Oh Kook-Hwan , Ahn Curie , Lee Kyu-Beck , Sung Su Ah 
Published: June 2017

AbstractThe clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011–2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b–5 but not in those with CKD stages 1–3a. Use of erythropoiesis-stimulating agents was associated with increased serum hepcidin levels, particularly in patients with CKD stages 3b–5 but not in those with CKD stages 1–3a, and serum hepcidin levels positively correlated with the dose of erythropoiesis-stimulating agent. These findings suggest that serum hepcidin may be a uremic toxin and play an important role in erythropoietin resistance. However, future prospective studies are needed to confirm our results.
Advantageous developmental outcomes of advancing paternal age
Authors: Janecka M , Rijsdijk F , Rai D , Modabbernia A , Reichenberg A 
Published: June 2017

AbstractAdvanced paternal age (APA) at conception has been associated with negative outcomes in offspring, raising concerns about increasing age at fatherhood. Evidence from evolutionary and psychological research, however, suggests possible link between APA and a phenotypic advantage. We defined such advantage as educational success, which is positively associated with future socioeconomic status. We hypothesised that high IQ, strong focus on the subject of interest and little concern about ‘fitting in’ will be associated with such success. Although these traits are continuously distributed in the population, they cluster together in so-called ‘geeks’. We used these measures to compute a ‘geek index’ (GI), and showed it to be strongly predictive of future academic attainment, beyond the independent contribution of the individual traits. GI was associated with paternal age in male offspring only, and mediated the positive effects of APA on education outcomes, in a similar sexually dimorphic manner. The association between paternal age and GI was partly mediated by genetic factors not correlated with age at fatherhood, suggesting contribution of de novo factors to the ‘geeky’ phenotype. Our study sheds new light on the multifaceted nature of the APA effects and explores the intricate links between APA, autism and talent.
Clinically Available Assessment Measures for Lingual and Labial Somatosensation in Healthy Adults: Normative Data and Test Reliability
Authors: Etter Nicole M. , Miller Olivia M. , Ballard Kirrie J. 
Published: June 2017

Purpose
High-quality orofacial somatosensory inputs are essential for achieving rapid and accurate motor outputs. Little somatosensory testing is currently being completed in clinical settings. The purpose of this study is to assess the feasibility and test–retest reliability of clinical assessment tools for orofacial somatosensory testing in healthy young adults.

Method

A total of 45 healthy young adults (ages 20–41 years) was recruited. Participants reported basic health information, completed pure-tone hearing thresholds, and were assessed using two-point discrimination discs and Von Frey hair detection and discrimination thresholds for bilateral lip and tongue. A subsample of participants (
n
= 18; 40%) returned to complete reliability testing.

Results
Descriptive results are presented for the normative group as well as the reliability group. Difference scores between Tests 1 and 2 for each testing measure and location show high agreement.

Conclusion
Two-point discrimination and Von Frey hair monofilament assessment for both detection- and discrimination-threshold estimates have high test–retest reliability in a healthy young population. These testing measures could be a way to easily complete objective somatosensory testing of the orofacial region in a clinical context.
The Effect of Stimulus Valence on Lexical Retrieval in Younger and Older Adults
Authors: Blackett Deena Schwen , Harnish Stacy M. , Lundine Jennifer P. , Zezinka Alexandra , Healy Eric W. 
Published: June 2017

Purpose
Although there is evidence that emotional valence of stimuli impacts lexical processes, there is limited work investigating its specific impact on lexical retrieval. The current study aimed to determine the degree to which emotional valence of pictured stimuli impacts naming latencies in healthy younger and older adults.

Method
Eighteen healthy younger adults and 18 healthy older adults named positive, negative, and neutral images, and reaction time was measured.

Results
Reaction times for positive and negative images were significantly longer than reaction times for neutral images. Reaction times for positive and negative images were not significantly different. Whereas older adults demonstrated significantly longer naming latencies overall than younger adults, the discrepancy in latency with age was far greater when naming emotional pictures.

Conclusions
Emotional arousal of pictures appears to impact naming latency in younger and older adults. We hypothesize that the increase in naming latency for emotional stimuli is the result of a necessary disengagement of attentional resources from the emotional images prior to completion of the naming task. We propose that this process may affect older adults disproportionately due to a decline in attentional resources as part of normal aging, combined with a greater attentional preference for emotional stimuli.