bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose tributyltin exposure induces an oxidative stress-triggered JNK-related pancreatic β-cell apoptosis and a reversible hypoinsulinemic hyperglycemia in mice
Authors: Huang Chun-Fa , Yang Ching-Yao , Tsai Jing-Ren , Wu Cheng-Tien , Liu Shing-Hwa , Lan Kuo-Cheng 
Published: April 2018

AbstractTributyltin (TBT), an endocrine disrupting chemical, can be found in food (particular in fish and seafood) and drinking water by contamination. Here, we elucidated the effects and possible mechanisms of low-dose TBT on the growth and function of pancreatic β-cells and glucose metabolism in mice. Submicromolar-concentration of TBT significantly induced β-cell cytotoxicity and apoptosis, which were accompanied by poly (ADP-ribose) polymerase cleavage and mitogen-activated protein kinases-JNK and ERK1/2 phosphorylation. TBT could also suppress the glucose-stimulated insulin secretion in β-cells and isolated mouse islets. TBT increased reactive oxygen species production. TBT-induced β-cell cytotoxicity and apoptosis were significantly prevented by antioxidant N-acetylcysteine (NAC) and JNK inhibitor SP600125, but not ERK1/2 inhibitor PD98059 and p38 inhibitor SB203580. Both NAC and SP600125 inhibited JNK phosphorylation and reduced cell viability in TBT-treated β-cells. Four-week exposure of TBT (0.25 mg/kg) to mice revealed the decreased plasma insulin, increased blood glucose and plasma malondialdehyde, suppressed islet insulin secretion, and increased islet caspase-3 activity, which could be reversed by NAC treatment. After removing the TBT exposure for 2 weeks, the TBT-induced glucose metabolism alteration was significantly reversed. These results suggest that low-dose TBT can induce β-cell apoptosis and interfere with glucose homeostasis via an oxidative stress-related pathway.
Endothelial Cell Phenotypes are Maintained During Angiogenesis in Cultured Microvascular Networks
Authors: Motherwell Jessica M. , Anderson Christopher R. , Murfee Walter L. 
Published: April 2018

AbstractA challenge in tissue engineering biomimetic models for studying angiogenesis is building the physiological complexity of real microvascular networks. Our laboratory recently introduced the rat mesentery culture model as an ex vivo experimental platform for investigating multicellular dynamics involved in angiogenesis within intact microvascular networks. The objective of this study was to compare endothelial cell phenotypes along capillary sprouts in cultured ex vivo rat mesentery microvascular networks to in vivo endothelial cell phenotypes. For Day 3 (Ex Vivo) tissues, adult rat mesentery tissues were cultured for three days in media supplemented with 10% serum. For Day 3 (In Vivo) tissues, adult rats were anesthetized and the mesentery was exteriorized for twenty minutes to induce angiogenesis. Microvascular networks from Day 3 (Ex Vivo) and Day 3 (In Vivo) groups were angiogenic, characterized by an increase in vessel density, capillary sprouting, and identification of similar BrdU-positive endothelial cell distributions along sprouts. Endothelial cells in both groups extended pseudopodia at the distal edge of capillary sprouts and displayed similar endothelial cell UNC5b, VEGFR-2, and CD36 labeling patterns. The results from this study support the physiological relevance of the rat mesentery culture model and highlight its novelty as a biomimetic tool for angiogenesis research.
Transverse dielectrophoretic-based DNA nanoscale confinement
Authors: Mahshid Sara , Lu Jia , Abidi Abrar A. , Sladek Robert , Reisner Walter W. , Ahamed Mohammed Jalal 
Published: April 2018

AbstractConfinement of single molecules within nanoscale environments is crucial in a range of fields, including biomedicine, genomics, and biophysics. Here, we present a method that can concentrate, confine, and linearly stretch DNA molecules within a single optical field of view using dielectrophoretic (DEP) force. The method can convert an open surface into one confining DNA molecules without a requirement for bonding, hydrodynamic or mechanical components. We use a transverse DEP field between a top coverslip and a bottom substrate, both of which are coated with a transparent conductive material. Both layers are attached using double-sided tape, defining the chamber. The nanofeatures lie at the “floor” and do not require any bonding. With the application of an alternating (AC) electric field (2 Vp-p) between the top and bottom electrodes, a DEP field gradient is established and used to concentrate, confine and linearly extend DNA in nanogrooves as small as 100-nm in width. We also demonstrate reversible loading/unloading of DNA molecules into nanogrooves and nanopits by switching frequency (between 10 kHz to 100 kHz). The technology presented in this paper provides a new method for single-molecule trapping and analysis.
Serpine1 Knockdown Enhances MMP Activity after Flexor Tendon Injury in Mice: Implications for Adhesions Therapy
Authors: Freeberg Margaret A. T. , Farhat Youssef M. , Easa Anas , Kallenbach Jacob G. , Malcolm Dominic W. , Buckley Mark R. , Benoit Danielle S. W. , Awad Hani A. 
Published: April 2018

AbstractInjuries to flexor tendons can be complicated by fibrotic adhesions, which severely impair the function of the hand. Adhesions have been associated with TGF-β1, which causes upregulation of PAI-1, a master suppressor of protease activity, including matrix metalloproteinases (MMP). In the present study, the effects of inhibiting PAI-1 in murine zone II flexor tendon injury were evaluated utilizing knockout (KO) mice and local nanoparticle-mediated siRNA delivery. In the PAI-1 KO murine model, reduced adherence of injured tendon to surrounding subcutaneous tissue and accelerated recovery of normal biomechanical properties compared to wild type controls were observed. Furthermore, MMP activity was significantly increased in the injured tendons of the PAI-1 KO mice, which could explain their reduced adhesions and accelerated remodeling. These data demonstrate that PAI-1 mediates fibrotic adhesions in injured flexor tendons by suppressing MMP activity. In vitro siRNA delivery to silence Serpine1 expression after treatment with TGF-β1 increased MMP activity. Nanoparticle-mediated delivery of siRNA targeting Serpine1 in injured flexor tendons significantly reduced target gene expression and subsequently increased MMP activity. Collectively, the data demonstrate that PAI-1 can be a druggable target for treating adhesions and accelerating the remodeling of flexor tendon injuries.
DNA-release by Streptococcus pneumoniae autolysin LytA induced Krueppel-like factor 4 expression in macrophages
Authors: Herta Toni , Bhattacharyya Aritra , Bollensdorf Christian , Kabus Christin , García Pedro , Suttorp Norbert , Hippenstiel Stefan , Zahlten Janine 
Published: April 2018

AbstractThe recruitment of myeloid cells to the lung is of utmost importance for the elimination of invading pathogens. We investigated the Streptococcus pneumoniae-dependent induction mechanism of KLF4 in macrophages as a potential regulator of the macrophage immune response. We demonstrated that only viable pneumococci, which have direct contact to the host cells and release LytA-dependent DNA, induced KLF4. Exogenous supplementation of pneumococcal, other bacterial, eukaryotic foreign (human) or self (mouse) DNA to autolysis-deficient pneumococci restored (at least in part) pneumococci-related KLF4 induction. Experiments using TLR9, TRIF and MyD88 knockout macrophages revealed that TLR9, TRIF and MyD88 were partly involved in the S. pneumoniae-induced KLF4 expression. BMMs missing important DNA receptor related molecules (ASC−/−, STING−/−) showed no differences in pneumococci-related KLF4 expression. Similar results were observed with IFNAR−/− BMMs and Type I IFN stimulated cells. LyzMcre mediated knockdown of KLF4 in BMMs resulted in a decreased secretion of proinflammatory cytokines and enhanced IL-10 release. In summary, we showed that pneumococci-related KLF4 induction in macrophages is mediated via a PAMP-DAMP induction mechanism involving a hitherto unknown host cell DNA sensor leading to a more proinflammatory macrophage phenotype.
An investigation of the mechanical and microstructural evolution of a TiNbZr alloy with varied ageing time
Authors: Biesiekierski Arne , Lin Jixing , Munir Khurram , Ozan Sertan , Li Yuncang , Wen Cuie 
Published: April 2018

AbstractAlloys comprised of the highly biocompatible elements titanium, niobium and zirconium have been a major focus in recent years in the field of metallic biomaterials. To contribute to the corpus of data in this field, the current paper presents results from a thorough microstructural and mechanical investigation of Ti-32Nb-6Zr subjected to a variety of ageing treatments. The presented alloy was stabilized to the higher temperature, body-centred cubic phase, showing only minimal precipitation on prolonged ageing, despite the presence of nanoscaled spinodal segregation arising from the Nb-Zr interaction. It further showed excellent mechanical properties, with tensile yield stresses as high as 820 MPa and Young’s moduli as low as 53 GPa. This leads to the ratio of strength to modulus, also known as the admissible strain, reaching a maximum of 1.3% after 6 hours ageing. These results are further supported by similar measurements from nanoindentation analysis.
The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of Kv1.3 to the plasma membrane
Authors: Voros Orsolya , Szilagyi Orsolya , Balajthy András , Somodi Sándor , Panyi Gyorgy , Hajdu Péter 
Published: April 2018

AbstractKv1.3 channels are expressed in several cell types including immune cells, such as T lymphocytes. The targeting of Kv1.3 to the plasma membrane is essential for T cell clonal expansion and assumed to be guided by the C-terminus of the channel. Using two point mutants of Kv1.3 with remarkably different features compared to the wild-type Kv1.3 (A413V and H399K having fast inactivation kinetics and tetraethylammonium-insensitivity, respectively) we showed that both Kv1.3 channel variants target to the membrane when the C-terminus was truncated right after the conserved HRET sequence and produce currents identical to those with a full-length C-terminus. The truncation before the HRET sequence (NOHRET channels) resulted in reduced membrane-targeting but non-functional phenotypes. NOHRET channels did not display gating currents, and coexpression with wild-type Kv1.3 did not rescue the NOHRET-A413V phenotype, no heteromeric current was observed. Interestingly, mutants of wild-type Kv1.3 lacking HRET(E) (deletion) or substituted with five alanines for the HRET(E) motif expressed current indistinguishable from the wild-type. These results demonstrate that the C-terminal region of Kv1.3 immediately proximal to the S6 helix is required for the activation gating and conduction, whereas the presence of the distal region of the C-terminus is not exclusively required for trafficking of Kv1.3 to the plasma membrane.
A retrospective study on association between obesity and cardiovascular risk diseases with aging in Chinese adults
Authors: Sun Jie , Zhou Weihong , Gu Tianwei , Zhu Dalong , Bi Yan 
Published: April 2018

AbstractThis study aimed to investigate the prevalence of overweight and obesity and its relationship with cardiovascular risk diseases among different sex and age groups in an urban Chinese adult population. A retrospective analysis was performed on 384,061 Chinese adults aged 20 years and older in Nanjing. The age-standardized prevalence of overweight and obesity was 42.8% and 13.2% in men and 23.9% and 6.6% in women. A gradually increasing trend was observed in the prevalence of overweight and obesity from 2008 to 2016, especially in individuals aged 20~39 years. Overweight and obesity were significantly associated with increased risks of dyslipidemia, diabetes mellitus, hypertension, and hyperuricemia. Age weakened such relationship for both genders, which spiked in individuals aged 20~39 years. For men and women aged 20~39 years, the OR (95% CI) of obesity reached 4.23 (4.01–4.47) and 5.29 (4.63–6.04) for dyslipidemia, 3.70 (2.97–4.60) and 6.38 (3.86–10.55) for diabetes mellitus, 6.19 (5.76–6.64) and 9.36 (7.86–11.13) for hypertension, and 3.66 (3.45–3.88) and 6.65 (5.70–7.74) for hyperuricemia, respectively. The increasing trend in the epidemic of overweight and obesity is a risk factor for cardiovascular risk diseases in Chinese adults, especially in individuals aged 20~39 years.
A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features
Authors: El-Sherbiny Y. M. , Psarras A. , Md Yusof M. Y. , Hensor E. M. A. , Tooze R. , Doody G. , Mohamed A. A. A , McGonagle D. , Wittmann M. , Emery P. , Vital E. M. 
Published: April 2018

AbstractMeasurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls. ISGs varied in response to IFN-subtypes and both scores varied between cell subsets. IFN-Score-A differentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p < 0.001), while IFN-Score-B differentiated SLE and RA from HC (both p < 0.001). In SLE, both scores were associated with cutaneous and hematological (all p < 0.05) but not musculoskeletal disease activity. Comparing with bimodal (IFN-high/low) classification, significant differences in IFN-scores were found between diagnostic groups within the IFN-high group. Our continuous 2-score system is more clinically relevant than a simple bimodal classification of IFN status. This system should allow improvement in diagnosis, stratification, and therapy in IFN-mediated autoimmunity.
Hedgehog Interacting Protein Promotes Fibrosis and Apoptosis in Glomerular Endothelial Cells in Murine Diabetes
Authors: Zhao Xin-Ping , Chang Shiao-Ying , Liao Min-Chun , Lo Chao-Sheng , Chenier Isabelle , Luo Hongyu , Chiasson Jean-Louis , Ingelfinger Julie R. , Chan John S. D. , Zhang Shao-Ling 
Published: April 2018

AbstractWe investigated whether renal hedgehog interacting protein (Hhip) expression contributes to the progression of diabetic nephropathy (DN) and studied its related mechanism(s) in vivo and in vitro. Here, we show that Hhip expression is highly elevated in glomerular endothelial cells of adult type 1 diabetic (T1D) Akita and T2D db/db mouse kidneys as compared to non-diabetic control littermates. Hyperglycemia enhances reactive oxygen species (ROS) generation via NADPH oxidase 4 (Nox4) activation and stimulates renal Hhip gene expression, and that elevated renal Hhip gene expression subsequently activates the TGFβ1- Smad2/3 cascade and promotes endothelial to mesenchymal transition associated with endothelial cell fibrosis/apoptosis in vivo and in vitro. Furthermore, kidneys of low-dose streptozotocin-induced diabetic heterozygous Hhip deficient (Hhip+/−) mice displayed a normal albumin/creatinine ratio with fewer features of DN (glomerulosclerosis/fibrosis and podocyte apoptosis/loss) and less evidence of renal compensation (glomerular hypertrophy and hyperfiltration) as compared to diabetic wild type controls (Hhip+/+). Thus, our studies demonstrated that renal Hhip expression is associated with nephropathy development in diabetes and that hyperglycemia-induced renal Hhip expression may mediate glomerular endothelial fibrosis and apoptosis in diabetes, a novel finding.
The role of stabilizing and communicating symptoms given overlapping communities in psychopathology networks
Authors: Blanken Tessa F. , Deserno Marie K. , Dalege Jonas , Borsboom Denny , Blanken Peter , Kerkhof Gerard A. , Cramer Angélique O. J. 
Published: April 2018

AbstractNetwork theory, as a theoretical and methodological framework, is energizing many research fields, among which clinical psychology and psychiatry. Fundamental to the network theory of psychopathology is the role of specific symptoms and their interactions. Current statistical tools, however, fail to fully capture this constitutional property. We propose community detection tools as a means to evaluate the complex network structure of psychopathology, free from its original boundaries of distinct disorders. Unique to this approach is that symptoms can belong to multiple communities. Using a large community sample and spanning a broad range of symptoms (Symptom Checklist-90-Revised), we identified 18 communities of interconnected symptoms. The differential role of symptoms within and between communities offers a framework to study the clinical concepts of comorbidity, heterogeneity and hallmark symptoms. Symptoms with many and strong connections within a community, defined as stabilizing symptoms, could be thought of as the core of a community, whereas symptoms that belong to multiple communities, defined as communicating symptoms, facilitate the communication between problem areas. We propose that defining symptoms on their stabilizing and/or communicating role within and across communities accelerates our understanding of these clinical phenomena, central to research and treatment of psychopathology.
Shorter sleep duration and better sleep quality are associated with greater tissue density in the brain
Authors: Takeuchi Hikaru , Taki Yasuyuki , Nouchi Rui , Yokoyama Ryoichi , Kotozaki Yuka , Nakagawa Seishu , Sekiguchi Atsushi , Iizuka Kunio , Yamamoto Yuki , Hanawa Sugiko , Araki Tsuyoshi , Miyauchi Carlos Makoto , Shinada Takamitsu , Sakaki Kohei , Nozawa Takayuki , Ikeda Shigeyuki , Yokota Susumu , Daniele Magistro , Sassa Yuko , Kawashima Ryuta 
Published: April 2018

AbstractPoor sleep quality is associated with unfavorable psychological measurements, whereas sleep duration has complex relationships with such measurements. The aim of this study was to identify the associations between microstructural properties of the brain and sleep duration/sleep quality in a young adult. The associations between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and sleep duration/sleep quality were investigated in a study cohort of 1201 normal young adults. Positive correlations between sleep duration and MD of widespread areas of the brain, including the prefrontal cortex (PFC) and the dopaminergic systems, were identified. Negative correlations between sleep quality and MD of the widespread areas of the brain, including the PFC and the right hippocampus, were also detected. Lower MD has been previously associated with more neural tissues in the brain. Further, shorter sleep duration was associated with greater persistence and executive functioning (lower Stroop interference), whereas good sleep quality was associated with states and traits relevant to positive affects. These results suggest that bad sleep quality and longer sleep duration were associated with aberrant neurocognitive measurements in the brain in healthy young adults.
A new way of producing pediocin in Pediococcus acidilactici through intracellular stimulation by internalized inulin nanoparticles
Authors: Kim Whee-Soo , Lee Jun-Yeong , Singh Bijay , Maharjan Sushila , Hong Liang , Lee Sang-Mok , Cui Lian-Hua , Lee Ki-June , Kim GiRak , Yun Cheol-Heui , Kang Sang-Kee , Choi Yun-Jaie , Cho Chong-Su 
Published: April 2018

AbstractOne of the most challenging aspects of probiotics as a replacement for antibiotics is to enhance their antimicrobial activity against pathogens. Given that prebiotics stimulate the growth and/or activity of probiotics, we developed phthalyl inulin nanoparticles (PINs) as prebiotics and observed their effects on the cellular and antimicrobial activities of Pediococcus acidilactici (PA). First, we assessed the internalization of PINs into PA. The internalization of PINs was largely regulated by glucose transporters in PA, and the process was energy-dependent. Once internalized, PINs induced PA to produce substantial amounts of antimicrobial peptide (pediocin), which is effective against both Gram-positive (Salmonella Gallinarum) and Gram-negative (Listeria monocytogenes) pathogens. When treated with small-sized PINs, PA witnessed a nine-fold increase in antimicrobial activity. The rise in pediocin activity in PA treated with PINs was accompanied by enhanced expression of stress response genes (groEL, groES, dnaK) and pediocin biosynthesis genes (pedA, pedD). Although the mechanism is not clear, it appears that the internalization of PINs by PA causes mild stress to activate the PA defense system, leading to increased production of pediocin. Overall, we identified a prebiotic in nanoparticle form for intracellular stimulation of probiotics, demonstrating a new avenue for the biological production of antimicrobial peptides.
Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease
Authors: Novati Arianna , Hentrich Thomas , Wassouf Zinah , Weber Jonasz J. , Yu-Taeger Libo , Déglon Nicole , Nguyen Huu Phuc , Schulze-Hentrich Julia M. 
Published: April 2018

AbstractHuntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene which results in progressive neurodegeneration in the striatum, cortex, and eventually most brain areas. Despite being a monogenic disorder, environmental factors influence HD characteristics. Both human and mouse studies suggest that mutant HTT (mHTT) leads to gene expression changes that harbor potential to be modulated by the environment. Yet, the underlying mechanisms integrating environmental cues into the gene regulatory program have remained largely unclear. To better understand gene-environment interactions in the context of mHTT, we employed RNA-seq to examine effects of maternal separation (MS) and environmental enrichment (EE) on striatal gene expression during development of BACHD rats. We integrated our results with striatal consensus modules defined on HTT-CAG length and age-dependent co-expression gene networks to relate the environmental factors with disease progression. While mHTT was the main determinant of expression changes, both MS and EE were capable of modulating these disturbances, resulting in distinctive and in several cases opposing effects of MS and EE on consensus modules. This bivalent response to maternal separation and environmental enrichment may aid in explaining their distinct effects observed on disease phenotypes in animal models of HD and related neurodegenerative disorders.