bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgenic mice overexpressing human TNF-α experience early onset spontaneous intervertebral disc herniation in the absence of overt degeneration
Authors: Gorth Deborah J. , Shapiro Irving M. , Risbud Makarand V. 
Published: December 2018

AbstractThere is a well-established link between cytokine expression and the progression of intervertebral disc degeneration. Among these cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are the most commonly studied. To investigate whether systemic hTNF-α overexpression affects intervertebral disc health, we studied the spine phenotype of Tg197 mice, a widely used hTNF-α transgenic line. These mice were studied at 12–16 weeks of age using comprehensive histochemical and immunohistological analysis of the spinal motion segment. Micro-CT analysis was performed to quantify vertebral trabecular bone architecture. The Tg197 mice evidenced spontaneous annular tears and herniation with increased vascularity in subchondral bone and significant immune cell infiltration. The full-thickness annular tear without nucleus pulposus (NP) extrusion resulted in neutrophil, macrophage, and mast cell infiltration into the disc, whereas the disc with full-thickness tear and pronounced NP herniation showed additional presence of CD4+ and CD8+ T cells. While the observed defects involved failure of the annular, endplate, and vertebral junction, there were no obvious alterations in the collagen or aggrecan content in the NP and annulus fibrosus or the maturity of collagen fibers in Tg197 mice. Despite elevated systemic inflammation and pronounced loss of trabecular bone in the vertebrae, intact Tg197 discs were healthy and showed an increase in NP cell number. The NP cells in intact discs preserved expression of phenotypic markers: CAIII, Glut1, and Krt19. In conclusion, elevated systemic TNF-α increases the susceptibility of mice to spontaneous disc herniation and possibly radiculopathy, without adversely affecting intact intervertebral disc health.
CUL1 promotes breast cancer metastasis through regulating EZH2-induced the autocrine expression of the cytokines CXCL8 and IL11
Authors: Huang Ye-Fei , Zhang Zhe , Zhang Meng , Chen Yan-Su , Song Jun , Hou Ping-Fu , Yong Hong-Mei , Zheng Jun-Nian , Bai Jin 
Published: December 2018

AbstractCUL1 is an essential component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Our previous study has showed that CUL1 is positively associated with poor overall and disease-specific survival of breast cancer patients. Here, we further explored its roles in breast cancer metastasis. Our data showed that CUL1 significantly promoted breast cancer cell migration, invasion, tube formation in vitro, as well as angiogenesis and metastasis in vivo. In mechanism, the human gene expression profiling was used to determine global transcriptional changes in MDA-MB-231 cells, and we identified autocrine expression of the cytokines CXCL8 and IL11 as the target genes of CUL1 in breast cancer cell migration, invasion, metastasis, and angiogenesis. CUL1 regulated EZH2 expression to promote the production of cytokines, and finally significantly aggravating the breast cancer cell metastasis and angiogenesis through the PI3K–AKT–mTOR signaling pathway. Combined with the previous report about CUL1, we proposed that CUL1 may serve as a promising therapeutic target for breast cancer metastasis.
Molecular and functional heterogeneity of IL-10-producing CD4+ T cells
Authors: Brockmann Leonie , Soukou Shiwa , Steglich Babett , Czarnewski Paulo , Zhao Lilan , Wende Sandra , Bedke Tanja , Ergen Can , Manthey Carolin , Agalioti Theodora , Geffken Maria , Seiz Oliver , Parigi Sara M. , Sorini Chiara , Geginat Jens , Fujio Keishi , Jacobs Thomas , Roesch Thomas , Izbicki Jacob R. , Lohse Ansgar W. , Flavell Richard A. , Krebs Christian , Gustafsson Jan-Ake , Antonson Per , Roncarolo Maria Grazia , Villablanca Eduardo J. , Gagliani Nicola , Huber Samuel 
Published: December 2018

AbstractIL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease demonstrate a deficiency in this specific regulatory T-cell subpopulation.
Author Correction: nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer
Authors: Ahn Ji-Hye , Lee Hyun-Sung , Lee Ju-Seog , Lee Yeon-Su , Park Jong-Lyul , Kim Seon-Young , Hwang Jung-Ah , Kunkeaw Nawapol , Jung Sung Yun , Kim Tae Jin , Lee Kwang-Soo , Jeon Sung Ho , Lee Inhan , Johnson Betty H. , Choi Jung-Hye , Lee Yong Sun 
Published: December 2018

In the original version of the Supplementary Information file associated with this Article, Supplementary Fig. 18 panel b was inadvertently replaced with a duplicate of panel a. The error has now been fixed and the corrected version of the Supplementary Information PDF is available to download from the HTML version of the Article.
Elevated hypertrophy, growth plate maturation, glycosaminoglycan deposition, and exostosis formation in the Hspg2 exon 3 null mouse intervertebral disc
Authors: Shu Cindy C. , Smith Susan M. , Little Christopher B. , Melrose James 
Published: December 2018

Abstract
Heparan sulfate (HS) regulates diverse cell signalling events in intervertebral disc development and homeostasis. The aim of the present study was to investigate the effect of ablation of perlecan HS/CS on murine intervertebral disc development. Genetic models carrying mutations in genes encoding HS biosynthetic enzymes have identified multiple roles for HS in tissue homeostasis. In the present study, we utilised an Hspg2 exon 3 null HS/CS-deficient mouse to assess the role of perlecan HS in disc cell regulation. HS makes many important contributions to growth factor sequestration, stabilisation/delivery, and activation of receptors directing cellular proliferation, differentiation, and assembly of extracellular matrix. Perlecan HS/CS-mediated interactions promote extracellular matrix assembly/stabilisation and tissue functional properties, and thus, removal of perlecan HS/CS should affect extracellular matrix function and homeostasis. Hspg2 exon 3 null intervertebral discs accumulated significantly greater glycosaminoglycan in the nucleus pulposus, annulus fibrosus, and vertebral growth plates than C57BL/6 wild-type (WT) I intervertebral discs. Proliferation of intervertebral disc progenitor cells was significantly higher in Hspg2 exon 3 null intervertebral discs, and these cells became hypertrophic by 12 weeks of age and were prominent in the vertebral growth plates but had a disorganised organisation. C57BL/6 WT vertebral growth plates contained regular columnar growth plate chondrocytes. Exostosis-like, ectopic bone formation occurred in Hspg2 exon 3 null intervertebral discs, and differences were evident in disc cell maturation and in matrix deposition in this genotype, indicating that perlecan HS/CS chains had cell and matrix interactive properties which repressively maintained tissue homeostasis in the adult intervertebral disc.
Spectroscopic membership for the populous 300 Myr-old open cluster NGC 3532
Authors: Fritzewski D. J. , Barnes S. A. , James D. J. , Geller A. M. , Meibom S. , Strassmeier K. G. 
Published: December 2018

Context. NGC 3532 is an extremely rich open cluster embedded in the Galactic disc, hitherto lacking a comprehensive, documented membership list.
Aims. We provide membership probabilities from new radial velocity observations of solar-type and low-mass stars in NGC 3532, in part as a prelude to a subsequent study of stellar rotation in the cluster.
Methods. Using extant optical and infra-red photometry we constructed a preliminary photometric membership catalogue, consisting of 2230 dwarf and turn-off stars. We selected 1060 of these for observation with the AAOmega spectrograph at the 3.9 m-Anglo-Australian Telescope and 391 stars for observations with the Hydra-South spectrograph at the 4 m Victor Blanco Telescope, obtaining spectroscopic observations over a decade for 145 stars. We measured radial velocities for our targets through cross-correlation with model spectra and standard stars, and supplemented them with radial velocities for 433 additional stars from the literature. We also measured log g, Teff, and [Fe/H] from the AAOmega spectra.
Results. The radial velocity distribution emerging from the observations is centred at 5.43 ± 0.04 km s−1 and has a width (standard deviation) of 1.46 km s−1. Together with proper motions from Gaia DR2 we find 660 exclusive members, of which five are likely binary members. The members are distributed across the whole cluster sequence, from giant stars to M dwarfs, making NGC 3532 one of the richest Galactic open clusters known to date, on par with the Pleiades. From further spectroscopic analysis of 153 dwarf members we find the metallicity to be marginally sub-solar, with [Fe/H] = −0.07 ± 0.10. We confirm the extremely low reddening of the cluster, EB − V = 0.034 ± 0.012 mag, despite its location near the Galactic plane. Exploiting trigonometric parallax measurements from Gaia DR2 we find a distance of 48435−30 pc [(m − M)0 = 8.42 ± 0.14 mag]. Based on the membership we provide an empirical cluster sequence in multiple photometric passbands. A comparison of the photometry of the measured cluster members with several recent model isochrones enables us to confirm the 300 Myr cluster age. However, all of the models evince departures from the cluster sequence in particular regions, especially in the lower mass range.
Auf den Spuren des Erb’schen Auskultationspunkts: Rätsel gelöst
Authors: Kolb Frederick , Spanke Johannes , Winkelmann Andreas 
Published: December 2018

Abstract“Erb’s point” is the fifth point of auscultation for the heart exam, located in the third intercostal space close to the sternum. It has sometimes been attributed to famous German neurologist Wilhelm Heinrich Erb (1840 – 1921), but without historical evidence. Erb’s focus on neurology suggested that the auscultation point may have been confused with other points in the neck named after Erb. As Erb was a specialist for neurological manifestations of syphilis, we speculated that the heart murmur of aortic incompetence produced by syphilitic aortitis, best heard at Erb’s point, linked Erb’s name to the auscultation point. However, we eventually found a publication by an American physician who visited Erb’s lectures in Heidelberg and reported that Erb explicitly introduced this “fifth point” in his case presentations in the late 1890 s. After all, Erb was chair of general medicine, with the first German chair of neurology only being established in 1919.
Demente Staatenlenker: Risiken und Nebenwirkungen
Authors: Förstl Hans 
Published: December 2018

AbstractIntellectually challenged heads of state have had a remarkable impact on the course of history and the problem of age-associated impairment in politicians appears to increase with growing life expectancy. Lenin, Paul Deschanel, Woodrow Wilson, Franklin D. Roosevelt, Heinrich Lübke, Urho Kekkonen, Mao tse tung, Ronald Reagan, Pope John Paul II., and Robert Mugabe were still in power while showing signs of cognitive impairment. Margaret Thatcher, Walter Scheel, Helmut Kohl and many others developed dementia after their resignation. Mild cognitive impairment in Paul von Hindenburg and in communist sclerocrats (Andropow, Breshnew, Ceausescu, Honecker, Mielke and others) may have contributed to the rise of Adolf Hitler and the downfall of communist regimes, respectively. Two prototypes of presidential dementia have to be distinguished: the tragic senile King-Lear-form with cognitive deficits and the buffalo- and buffoon-like King-Ubu-type with predominant behavioral disturbances.
Santiago Ramón y Cajal – Neuroanatom, Künstler und Literat
Authors: Steininger Helmuth , Codina-Canet Carolina 
Published: December 2018

AbstractSantiago Ramón y Cajal came from North Spain and was very talented in painting and writing. Actually he wanted to become a painter but his father, who was a medical doctor himself, forced him to study medicine. In the end, he became a famous neuroanatomist, developed the neuron theory and, together with Camillo Golgi, was awarded the Nobel Price for medicine in 1906. In his career, he was very much supported by German scientists, especially by the Würzburg anatomist von Koelliker. He also displayed a lively literary activity. But most of his works are little known to us. Of his 5 “Cuentos de vacaciones” (vacation stories) there is a translation into English only since 2001.
Rezept für Bewegung in der Nephrologie
Authors: Löllgen Herbert , Krause Rolfdieter , Zupet Petra , Degenhardt Stefan 
Published: December 2018

ZusammenfassungDie Behandlung der chronischen Niereninsuffizienz (chronic kidney disease, CKD)
in Klinik und Praxis, auch unter der Dialysetherapie, beinhaltet stets eine
umfangreiche medikamentöse Gabe und eine regelmäßige Überwachung. Die
Niereninsuffizienz als chronische Erkrankung gehört zu der Gruppe von
Krankheiten, die auch von einer nicht medikamentösen Therapie profitiert –
nämlich von einer regelmäßigen körperlichen Aktivität. Trotz zahlreicher
Publikationen zu diesem Thema werden Bewegung und körperliche Aktivität noch zu
wenig bei Patienten mit CKD eingesetzt. Mit den Ergebnissen des Trainings
während der Dialyse und dem Rezept für Bewegung gibt es effektive Ansätze, die
Faktoren des gesunden Lebensstils in das Behandlungskonzept bei Nierenpatienten
einzusetzen.
An Update on Addison’s Disease
Authors: Barthel Andreas , Benker Georg , Berens Kai , Diederich Sven , Manfras Burkhard , Gruber Matthias , Kanczkowski Waldemar , Kline Greg , Kamvissi-Lorenz Virginia , Hahner Stefanie , Beuschlein Felix , Brennand Ana , Boehm Bernhard , Torpy David , Bornstein Stefan 
Published: December 2018

AbstractAddison’s disease – the traditional term for primary adrenal insufficiency (PAI) – is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. In addition to the common “classical” causes of PAI like autoimmune, infectious, neoplastic and genetic disorders, other iatrogenic conditions – mostly pharmacological side effects (e. g., adrenal haemorrhage associated with anticoagulants, drugs affecting glucocorticoid synthesis, action or metabolism and some of the novel anti-cancer checkpoint inhibitors) are contributing factors to this phenomenon.Due to the rarity of the disease and often non-specific symptoms at least in the early stages, PAI is frequently not considered resulting in a delayed diagnosis. Successful therapy is mainly based on adequate patient education as a cornerstone in the prevention and management of adrenal crisis. A focus of current research is in the development of pharmacokinetically optimized glucocorticoid preparations as well as regenerative therapies.
Multiple kartilaginäre Exostosen
Authors: Schmidt A. 
Published: December 2018

ZusammenfassungAls multiple kartilaginäre Exostosen bezeichnet man bei einer Inzidenz von 1:50 000 eine einem autosomal-dominanten Erbgang unterliegende tumorähnliche Erkrankung des Knochen in Gestalt von zahlreichen, meist gutartigen, knorpelbedeckten Osteochondromen. Bei selten einem völlig asymptomatischen Verlauf werden die klinischen Probleme durch die von typischen Fehlstellungen und Deformitäten verursachten funktionellen Einschränkungen geprägt sowie nach Pedrini klassifiziert. Anhand der Kasuistik eines 45-jährigen Mannes erfolgt beispielhaft eine gutachterliche Einschätzungsempfehlung aus dem Schwerbehindertenrecht.
AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis
Authors: Cordero-Herrera Isabel , Kozyra Mikael , Zhuge Zhengbing , McCann Haworth Sarah , Moretti Chiara , Peleli Maria , Caldeira-Dias Mayara , Jahandideh Arghavan , Huirong Han , Cruz Josiane de Campos , Kleschyov Andrei L. , Montenegro Marcelo F. , Ingelman-Sundberg Magnus , Weitzberg Eddie , Lundberg Jon O. , Carlstrom Mattias 
Published: December 2018

Significance
Liver steatosis, or fatty liver, is the most common liver disease in the world, affecting up to 25% of all Americans. There is currently no approved drug available for this condition, which may progress to serious disease, including steatohepatitis, fibrosis, and cirrhosis. Here, we show in rodent and human models of metabolic syndrome that steatosis can be prevented by a simple dietary approach. Inorganic nitrate, present in green leafy vegetables, is converted in vivo to nitric oxide (NO) in a process involving symbiotic host bacteria. NO then induces key metabolic regulatory pathways to ultimately reduce oxidative stress and improve cardiometabolic functions. Clinical trials would be helpful to tell if dietary nitrate is useful in treatment and prevention of fatty liver disease.
Near doubling of Brazil’s intensive row crop area since 2000
Authors: Zalles Viviana , Hansen Matthew C. , Potapov Peter V. , Stehman Stephen V. , Tyukavina Alexandra , Pickens Amy , Song Xiao-Peng , Adusei Bernard , Okpa Chima , Aguilar Ricardo , John Nicholas , Chavez Selena 
Published: December 2018

Significance
As Brazil’s cropland expands as a result of increasing demand for commodity crops, new croplands replace existing land covers and land uses. Our study employs the most spatially detailed historical record of satellite imagery available to show that the area of intensive row cropping in Brazil nearly doubled from 2000 to 2014 mainly because of the repurposing of pastures (80% of new cropland) rather than conversion of natural vegetation (20%). Trends of cropland expansion through time may be linked to land use policies, market conditions, and other factors. Although evidence suggests that land use policies slowed cropland expansion within Amazon rainforests, no such decrease was found for Cerrado savannas, which experienced 2.5 times the natural vegetation conversion of the Amazon biome.
Research progress in protein posttranslational modification site prediction
Authors: He Wenying , Wei Leyi , Zou Quan 
Published: December 2018

AbstractPosttranslational modifications (PTMs) play an important role in regulating protein folding, activity and function and are involved in almost all cellular processes. Identification of PTMs of proteins is the basis for elucidating the mechanisms of cell biology and disease treatments. Compared with the laboriousness of equivalent experimental work, PTM prediction using various machine-learning methods can provide accurate, simple and rapid research solutions and generate valuable information for further laboratory studies. In this review, we manually curate most of the bioinformatics tools published since 2008. We also summarize the approaches for predicting ubiquitination sites and glycosylation sites. Moreover, we discuss the challenges of current PTM bioinformatics tools and look forward to future research possibilities.
Controlled Human Malaria Infection of Healthy Adults With Lifelong Malaria Exposure to Assess Safety, Immunogenicity, and Efficacy of the Asexual Blood Stage Malaria Vaccine Candidate GMZ2
Authors: Dejon-Agobe Jean Claude , Ateba-Ngoa Ulysse , Lalremruata Albert , Homoet Andreas , Engelhorn Julie , Nouatin Odilon Paterne , Edoa Jean Ronald , Fernandes José F , Esen Meral , Mouwenda Yoanne Darelle , Betouke Ongwe Eunice M , Massinga-Loembe Marguerite , Hoffman Stephen L , Sim B Kim Lee , Theisen Michael , Kremsner Peter G , Adegnika Ayôla A , Lell Bertrand , Mordmüller Benjamin 
Published: December 2018

AbstractBackgroundGMZ2 is a recombinant malaria vaccine inducing immune responses against Plasmodium falciparum (Pf) merozoite surface protein-3 and glutamate-rich protein. We used standardized controlled human malaria infection (CHMI) to assess the efficacy of this asexual blood-stage vaccine.MethodsWe vaccinated 50 healthy, adult volunteers with lifelong exposure to Pf 3 times, at 4-week intervals, with 30 or 100 µg GMZ2 formulated in CAF01, a liposome-based adjuvant; 100 µg GMZ2, formulated in Alhydrogel; or a control vaccine (Verorab). Approximately 13 weeks after the last vaccination, 35/50 volunteers underwent CHMI by direct venous inoculation of 3200 Pf sporozoites (Sanaria® PfSPZ Challenge).ResultsAdverse events were similarly distributed between GMZ2 and control vaccinees. Baseline-corrected anti-GMZ2 antibody concentrations 4 weeks after the last vaccination were higher in all 3 GMZ2-vaccinated arms, compared to the control group. All GMZ2 formulations induced similar antibody levels. CHMI resulted in 29/34 (85%) volunteers with Pf parasitemia and 15/34 (44%) with malaria (parasitemia and symptoms). The proportion of participants with malaria (2/5 control, 6/10 GMZ2-Alhydrogel, 2/8 30 µg GMZ2-CAF01, and 5/11 100 µg GMZ2-CAF01) and the time it took them to develop malaria were similar in all groups. Baseline, vaccine-specific antibody concentrations were associated with protection against malaria.ConclusionsGMZ2 is well tolerated and immunogenic in lifelong–Pf-exposed adults from Gabon, with similar antibody responses regardless of formulation. CHMI showed no protective effect of prior vaccination with GMZ2, although baseline, vaccine-specific antibody concentrations were associated with protection. CHMI with the PfSPZ Challenge is a potent new tool to validate asexual, blood-stage malaria vaccines in Africa.Clinical Trials RegistrationPan-African Clinical Trials: PACTR201503001038304