bluuebunny/crossref_metadata_2025_split huggingface dataset:
NemaLife chip: a micropillar-based microfluidic culture device optimized for aging studies in crawling C. elegans
Authors: Rahman Mizanur , Edwards Hunter , Birze Nikolajs , Gabrilska Rebecca , Rumbaugh Kendra P. , Blawzdziewicz Jerzy , Szewczyk Nathaniel J. , Driscoll Monica , Vanapalli Siva A. 
Published: October 2020

AbstractIn this study, we report a microfluidic device for the whole-life culture of the nematode Caenorhabditis elegans that allows the scoring of animal survival and health measures. This device referred to as the NemaLife chip features: (1) an optimized micropillar arena in which animals can crawl, (2) sieve channels that separate progeny and prevent the loss of adults from the arena during culture maintenance, and (3) ports that allow rapid accessibility for feeding the adult-only population and introducing reagents as needed. The pillar arena geometry was optimized to accommodate the growing body size during culture and emulate the body gait and locomotion of animals reared on agar. Likewise, feeding protocols were optimized to recapitulate longevity outcomes typical of standard plate growth. Key benefits of the NemaLife Chip include eliminating the need to perform repeated manual transfers of adults during survival assays, negating the need for progeny-blocking chemical interventions, and avoiding the swim-induced stress across lifespan in animals reared in liquid. We also show that the culture of animals in pillar-less microfluidic chambers reduces lifespan and introduces physiological stress by increasing the occurrence of age-related vulval integrity disorder. We validated our pillar-based device with longevity analyses of classical aging mutants (daf-2, age-1, eat-2, and daf-16) and animals subjected to RNAi knockdown of age-related genes (age-1 and daf-16). We also showed that healthspan measures such as pharyngeal pumping and tap-induced stimulated reversals can be scored across the lifespan in the NemaLife chip. Overall, the capacity to generate reliable lifespan and physiological data underscores the potential of the NemaLife chip to accelerate healthspan and lifespan investigations in C. elegans.
Sclerostin antibody stimulates periodontal regeneration in large alveolar bone defects
Authors: Yao Yao , Kauffmann Frederic , Maekawa Shogo , Sarment Lea V. , Sugai James V. , Schmiedeler Caroline A. , Doherty Edward J. , Holdsworth Gill , Kostenuik Paul J. , Giannobile William V. 
Published: October 2020

AbstractDestruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.
A study of associations between CUBN, HNF1A, and LIPC gene polymorphisms and coronary artery disease
Authors: Park Han Sung , Kim In Jai , Kim Eun Gyo , Ryu Chang Soo , Lee Jeong Yong , Ko Eun Ju , Park Hyeon Woo , Sung Jung Hoon , Kim Nam Keun 
Published: October 2020

AbstractThe aim of this study was to identify novel genetic markers related to coronary artery disease (CAD) using a whole-exome sequencing (WES) approach and determine any associations between the selected gene polymorphisms and CAD prevalence. CUBN, HNF1A and LIPC gene polymorphisms related to CAD susceptibility were identified using WES screening. Possible associations between the five gene polymorphisms and CAD susceptibility were examined in 452 CAD patients and 421 control subjects. Multivariate logistic regression analyses indicated that the CUBN rs2291521GA and HNF1A rs55783344CT genotypes were associated with CAD (GG vs. GA; adjusted odds ratio [AOR] = 1.530; 95% confidence interval [CI] 1.113–2.103; P = 0.002 and CC vs. CT; AOR = 1.512; 95% CI 1.119–2.045; P = 0.007, respectively). The CUBN rs2291521GA and HNF1A rs55783344CT genotype combinations exhibited a stronger association with CAD risk (AOR = 2.622; 95% CI 1.518–4.526; P = 0.001). Gene-environment combinatorial analyses indicated that the CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotype combination and several clinical factors (fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels) were associated with increased CAD risk. The CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotypes in conjunction with abnormally elevated cholesterol levels increase the risk of developing CAD. This exploratory study suggests that polymorphisms in the CUBN, HNF1A, and LIPC genes can be useful biomarkers for CAD diagnosis and treatment.
Microbiological and host-derived biomarker evaluation following non-surgical periodontal therapy with short-term administration of systemic antimicrobials: secondary outcomes of an RCT
Authors: Cosgarea Raluca , Eick S. , Jepsen S. , Arweiler N. B. , Juncar R. , Tristiu R. , Salvi G. E. , Heumann C. , Sculean A. 
Published: October 2020

AbstractNonsurgical periodontal therapy with adjunctive use of systemic antimicrobials (for 7–14 days) showed improved clinical, microbiological and immunological results over the mechanical protocol alone. Considering the increasing risk for antimicrobial resistance with longer antibiotic regimes, it is important to establish the optimal antibiotic protocol with a maximum antimicrobial benefit and minimum risk for adverse effects. The aim of the study was to evaluate the microbiological and inflammatory outcomes 12-months after a 3-/7-day systemic antibiotic protocol [amoxicillin (AMX) + metronidazole (MET)] adjunctive to subgingival debridement in severe periodontitis compared to mechanical treatment alone. From the initially treated 102 patients, 75 subjects (Placebo group: n = 26; 3-day AMX + MET group: n = 24; 7-day AMX + MET group: n = 25) completed the 12-month examination. Clinical parameters, eight periodontal pathogens and inflammatory markers were determined at baseline and 3-, 6-, 12-months after therapy using real-time PCR and ELISA respectively. After 6 months, several periodontopathogens were significantly more reduced in the two antibiotic groups compared to placebo (p < 0.05). After 1 year, both antibiotic protocols showed significant reductions and detection of the keystone pathogen P. gingivalis compared to placebo. Antibiotic protocols, smoking, disease severity, baseline-BOP, -CAL and -IL-1β, as well as detection of T. denticola at 12-months significantly influenced the residual number of deep sites. The present data indicate that the systemic use of both short and longer antibiotic protocols (AMX + MET) adjunctive to nonsurgical periodontal therapy lead to higher microbiological improvements compared to subgingival debridement alone. The two investigated antibiotic protocols led to comparable microbiological and inflammatory results.
Metformin enhances protection in guinea pigs chronically infected with Mycobacterium tuberculosis
Authors: Frenkel Jessica D. Haugen , Ackart David F. , Todd Alexandra K. , DiLisio James E. , Hoffman Siana , Tanner Samantha , Kiran Dilara , Murray Megan , Chicco Adam , Obregón-Henao Andrés , Podell Brendan K. , Basaraba Randall J. 
Published: October 2020

AbstractTuberculosis (TB) is a chronic inflammatory disease that is often associated with alterations in systemic and cellular metabolism that resolves following successful antimicrobial drug treatment. We hypothesized that altered systemic glucose metabolism as a consequence of Mycobacterium tuberculosis (Mtb) infection, contributes to TB pathogenesis, and when normalized with anti-glycemic drugs would improve clinical outcomes. To test this hypothesis, guinea pigs were treated daily with the anti-diabetic drug metformin starting 4 weeks prior or concurrent with aerosol exposure to the H37Rv strain of Mtb. In the chronic stages of infection, Mtb infected metformin-treated animals had restored systemic insulin sensitivity but remained glucose intolerant as determined by oral glucose tolerance testing. Despite persistent glucose intolerance, metformin-treated guinea pigs had a 2.8-fold reduction in lung lesion burden and a 0.7 log decrease in CFUs. An alternative hypothesis that metformin treatment improved clinical disease by having a direct effect on immune cell energy metabolism was tested using extracellular flux analysis and flow cytometry. The proinflammatory immune response to Mtb infection in untreated guinea pigs was associated with a marked increase in energy metabolism (glycolysis and mitochondrial respiration) of peripheral blood mononuclear cells (PBMCs), which was normalized in metformin-treated guinea pigs. Moreover, both CD4+ and CD8+ T lymphocytes from Mtb infected, metformin treated animals maintained a more normal mitochondrial membrane potential while those isolated from untreated animals had persistent mitochondrial hyperpolarization. These data suggest that metformin promotes natural host resistance to Mtb infection by maintaining immune cell metabolic homeostasis and function during the chronic stages of active TB disease.
Protein-N-myristoylation-dependent phosphorylation of serine 13 of tyrosine kinase Lyn by casein kinase 1γ at the Golgi during intracellular protein traffic
Authors: Kinoshita-Kikuta Emiko , Utsumi Toshihiko , Miyazaki Aya , Tokumoto Chiharu , Doi Kyosuke , Harada Haruna , Kinoshita Eiji , Koike Tohru 
Published: October 2020

AbstractProtein N-myristoylation of Src-family kinases (SFKs) is a critical co-translational modification to anchor the enzymes in the plasma membrane. Phosphorylation of SFKs is also an essential modification for regulating their enzymatic activities. In this study, we used Phos-tag SDS-PAGE to investigate N-myristoylation-dependent phosphorylation of SFKs and their non-N-myristoylated G2A mutants. The serine-13 residue of Lyn (Lyn-S13) was shown to be N-myristoylation-dependently phosphorylated. Although there have been more than 40 reports of mass spectrometric studies on phosphorylation at Lyn-S13, the kinase responsible remained unclear. We succeeded in identifying casein kinase 1γ (CK1γ) as the kinase responsible for phosphorylation of Lyn-S13. In HEK293 cells co-expressing Lyn and CK1γ, the phosphorylation level of Lyn-S13 increased significantly. CK1γ is unique among the CK1 family (α, γ, δ, and ε) in carrying an S-palmitoylation site for membrane binding. Co-expression with the non-S-palmitoylated CK1γ mutant, which localized in the cytosol, gave no increase in the phosphorylation level at Lyn-S13. In HEK293 cells expressing the non-S-palmitoylated Lyn-C3A mutant, on the other hand, the Lyn-C3A mutant was phosphorylated at Lyn-S13, and the mutant remained at the Golgi. These results showed that S-palmitoylated CK1γ can phosphorylate S13 of N-myristoylated Lyn at the Golgi during intracellular protein traffic.
The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells
Authors: Glorieux Mary , Dok Rüveyda , Nuyts Sandra 
Published: October 2020

AbstractRadiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Here, the influence of PI3K pathway inhibition on radiotherapy response was investigated. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. Despite targeted inhibition of the pathway and slight increase in DNA damage, PI3K inhibition did not show significant radiosensitization. Currently only one clinical trial is assessing the effectiveness of combining BKM120 with RT in HNSCC (NCT02113878) of which the results are eagerly awaited.
New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids
Authors: Lees Rosemary S. , Ismail Hanafy M. , Logan Rhiannon A. E. , Malone David , Davies Rachel , Anthousi Amalia , Adolfi Adriana , Lycett Gareth J. , Paine Mark J. I. 
Published: October 2020

AbstractFenazaquin, pyridaben, tolfenpyrad and fenpyroximate are Complex I inhibitors offering a new mode of action for insecticidal malaria vector control. However, extended exposure to pyrethroid based products such as long-lasting insecticidal nets (LLINs) has created mosquito populations that are largely pyrethroid-resistant, often with elevated levels of P450s that can metabolise and neutralise diverse substrates. To assess cross-resistance liabilities of the Complex I inhibitors, we profiled their susceptibility to metabolism by P450s associated with pyrethroid resistance in Anopheles gambiae (CYPs 6M2, 6P3, 6P4, 6P5, 9J5, 9K1, 6Z2) and An. funestus (CYP6P9a). All compounds were highly susceptible. Transgenic An. gambiae overexpressing CYP6M2 or CYP6P3 showed reduced mortality when exposed to fenpyroximate and tolfenpyrad. Mortality from fenpyroximate was also reduced in pyrethroid-resistant strains of An. gambiae (VK7 2014 and Tiassalé 13) and An. funestus (FUMOZ-R). P450 inhibitor piperonyl butoxide (PBO) significantly enhanced the efficacy of fenpyroximate and tolfenpyrad, fully restoring mortality in fenpyroximate-exposed FUMOZ-R. Overall, results suggest that in vivo and in vitro assays are a useful guide in the development of new vector control products, and that the Complex I inhibitors tested are susceptible to metabolic cross-resistance and may lack efficacy in controlling pyrethroid resistant mosquitoes.
Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis
Authors: Banaganapalli Babajan , Mansour Haifa , Mohammed Arif , Alharthi Arwa Mastoor , Aljuaid Nada Mohammed , Nasser Khalidah Khalid , Ahmad Aftab , Saadah Omar I. , Al-Aama Jumana Yousuf , Elango Ramu , Shaik Noor Ahmad 
Published: October 2020

AbstractCeliac disease (CeD) is a gastrointestinal autoimmune disorder, whose specific molecular basis is not yet fully interpreted. Therefore, in this study, we compared the global gene expression profile of duodenum tissues from CeD patients, both at the time of disease diagnosis and after two years of the gluten-free diet. A series of advanced systems biology approaches like differential gene expression, protein–protein interactions, gene network-cluster analysis were deployed to annotate the candidate pathways relevant to CeD pathogenesis. The duodenum tissues from CeD patients revealed the differential expression of 106 up- and 193 down-regulated genes. The pathway enrichment of differentially expressed genes (DEGs) highlights the involvement of biological pathways related to loss of cell division regulation (cell cycle, p53 signalling pathway), immune system processes (NOD-like receptor signalling pathway, Th1, and Th2 cell differentiation, IL-17 signalling pathway) and impaired metabolism and absorption (mineral and vitamin absorptions and drug metabolism) in celiac disease. The molecular dysfunctions of these 3 biological events tend to increase the number of intraepithelial lymphocytes (IELs) and villous atrophy of the duodenal mucosa promoting the development of CeD. For the first time, this study highlights the involvement of aberrant cell division, immune system, absorption, and metabolism pathways in CeD pathophysiology and presents potential novel therapeutic opportunities.
Evidence of motor injury due to damaged corticospinal tract following acute hemorrhage in the basal ganglia region
Authors: Li Jing , Wei Xue Hu , Liu Yong Kang , Chen Ling Shan , Zhu Zheng Qiu , Hou Si Yuan , Fang Xiao Kun , Wang Zhong Qiu 
Published: October 2020

AbstractThe integrity of the corticospinal tract (CST) is significantly affected following basal ganglia haemorrhage. We aimed to assess the local features of CST and to effectively predict motor function by diffusion characteristics of CST in patients with motor injury following acute haemorrhage in the acute basal ganglia region. We recruited 37 patients with paresis of the lateral limbs caused by acute basal ganglia haemorrhage. Based on the automated fiber quantification method to track CST, assessed the character of each CST segment between the affected and contralateral sides, and correlated these with the Fugl–Meyer (FM) and Barthel Index (BI) scores at 6 months after onset. The fractional anisotropy (FA) values of the injured side of CST showed a significantly lower FA than the contralateral side along the tract profiles (p < 0.05, corrections for multiple comparisons). The FA values of each site at the internal capsule, closed corona radiata were positively correlated with the FM and BI score at 6 months after onset (p < 0.001, respectively). Our findings assessed the character of CST vividly in detail and dementated the primary sites of CST can predict the long-term outcome of motor function. This study may facilitate future clinical and cognitive studies of acute haemorrhage.
Lifelong smoking trajectories of Northern Finns are characterized by sociodemographic and lifestyle differences in a 46-year follow-up
Authors: Oura Petteri , Rissanen Ina , Junno Juho-Antti , Harju Terttu , Paananen Markus 
Published: October 2020

AbstractSmoking remains among the leading causes of mortality worldwide. Obtaining a comprehensive understanding of a population’s smoking behaviour is essential for tobacco control. Here, we aim to characterize lifelong smoking patterns and explore underlying sociodemographic and lifestyle factors in a population-based birth cohort population followed up for 46 years. Our analysis is based on 5797 individuals from the Northern Finland Birth Cohort 1966 who self-reported their tobacco smoking behaviour at the ages of 14, 31 and 46. Data on sex, education, employment, body mass index, physical activity, alcohol consumption, and substance addiction were also collected at the follow-ups. We profile each individual’s annual smoking history from the age of 5 to 47, and conduct a latent class trajectory analysis on the data. We then characterize the identified smoking trajectory classes in terms of the background variables, and compare the heaviest smokers with other classes in order to reveal specific predictors of non-smoking and discontinued smoking. Six smoking trajectories are identified in our sample: never-smokers (class size 41.0%), youth smokers (12.6%), young adult quitters (10.8%), late adult quitters (10.5%), late starters (4.3%), and lifetime smokers (20.7%). Smoking is generally associated with male sex, lower socioeconomic status and unhealthier lifestyle. Multivariable between-class comparisons identify unemployment (odds ratio [OR] 1.28–1.45) and physical inactivity (OR 1.20–1.52) as significant predictors of lifetime smoking relative to any other class. Female sex increases the odds of never-smoking and youth smoking (OR 1.29–1.33), and male sex increases the odds of adult quitting (OR 1.30–1.41), relative to lifetime smoking. We expect future initiatives to benefit from our data by exploiting the identified predictors as direct targets of intervention, or as a means of identifying individuals who may benefit from such interventions.
Elevated adipose tissue associated IL-2 expression in obesity correlates with metabolic inflammation and insulin resistance
Authors: Kochumon Shihab , Al Madhoun Ashraf , Al-Rashed Fatema , Thomas Reeby , Sindhu Sardar , Al-Ozairi Ebaa , Al-Mulla Fahd , Ahmad Rasheed 
Published: October 2020

AbstractAdipose tissue (AT) associated cytokines are involved in the development of chronic low-grade inflammation in obese individuals. IL-2, a pleiotropic cytokine, contributes to immune alterations during inflammation. However, the interaction between AT-IL-2 and other inflammatory biomolecules in obesity remains elusive. We investigated whether AT-IL-2 expression was associated with markers of inflammation and insulin resistance in overweight/obese individuals. Subcutaneous fat tissues were collected from 56 individuals (lean/overweight/obese) for RNA extraction. IL-2 and inflammatory mediators were quantified by qRT-PCR and immunohistochemistry. CRP was measured by ELISA. AT-IL-2 expression was higher in obese compared with lean individuals (P < 0.021) and correlated with BMI. IL-2 correlated with interleukins IL-8 and IL-12A (r = 0.333–0.481; p = 0.0001–0.029); as well as with chemokines and their receptors including CCL5, CCL19, CCR2 and CCR5 (r = 0.538–0.677; p < 0.0001). Moreover, IL-2 correlated with toll-like receptors (TLR2, TLR8, TLR10), interferon regulatory factor 5 (IRF5) and cluster of differentiation CD11c (r = 0.282–0.357; p < 0.039). Notably, IL-2 was associated positively with fasting blood glucose (FBG), HbA1c, TGL and CRP (r ≥ 0.423;P ≤ 0.007). In multiple regression analysis, IL-2 is an independent predictor of IL-8, IL-12A, TLR10, TGL and HbA1c. Overall, our data demonstrate that increased expression of the AT-IL-2, in obesity, may represent a novel biomarker for progression of metabolic inflammation and insulin-resistance.
Endometriosis and chronic pelvic pain have similar impact on women, but time to diagnosis is decreasing: an Australian survey
Authors: Armour Mike , Sinclair Justin , Ng Cecilia H. M. , Hyman Mikayla S. , Lawson Kenny , Smith Caroline A. , Abbott Jason 
Published: October 2020

AbstractChronic pelvic pain (CPP) affects a significant number of women worldwide. Internationally, people with endometriosis report significant negative impact across many areas of their life. We aimed to use an online survey using the EndoCost tool to determine if there was any difference in the impact of CPP in those with vs. those without a confirmed diagnosis of endometriosis, and if there was any change in diagnostic delay since the introduction of clinical guidelines in 2005. 409 responses were received; 340 with a diagnosis of endometriosis and 69 with no diagnosis. People with CPP, regardless of diagnosis, reported moderate to severe dysmenorrhea and non-cyclical pelvic pain. Dyspareunia was also common. Significant negative impact was reported for social, academic, and sexual/romantic relationships in both cohorts. In the endometriosis cohort there was a mean diagnostic delay of eight years, however there was a reduction in both the diagnostic delay (p < 0.001) and number of doctors seen before diagnosis (p < 0.001) in those presenting more recently. Both endometriosis and CPP have significant negative impact. Whilst there is a decrease in the time to diagnosis, there is an urgent need for improved treatment options and support for women with the disease once the diagnosis is made.