bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down-regulation of CK2α correlates with decreased expression levels of DNA replication minichromosome maintenance protein complex (MCM) genes
Authors: Schaefer Susanne , Doktor Thomas K. , Frederiksen Sabrina B. , Chea Kathleen , Hlavacova Mirka , Bruun Gitte H. , Rabjerg Maj , Andresen Brage S. , Dominguez Isabel , Guerra Barbara 
Published: October 2019

AbstractProtein kinase CK2 is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α’) and two regulatory subunits (CK2β). It is implicated in every stage of the cell cycle and in the regulation of various intracellular pathways associated with health and disease states. The catalytic subunits have similar biochemical activity, however, their functions may differ significantly in cells andin vivo. In this regard, homozygous deletion ofCK2αleads to embryonic lethality in mid-gestation potentially due to severely impaired cell proliferation. To determine the CK2α-dependent molecular mechanisms that control cell proliferation, we established a myoblast-derived cell line with inducible silencing of CK2α and carried out a comprehensive RNA-Seq analysis of gene expression. We report evidence that CK2α depletion causes delayed cell cycle progression through the S-phase and defective response to replication stress. Differential gene expression analysis revealed that the down-regulated genes were enriched in pathways implicated in cell cycle regulation, DNA replication and DNA damage repair. Interestingly, the genes coding for the minichromosome maintenance proteins (MCMs), which constitute the core of the replication origin recognition complex, were among the most significantly down-regulated genes. These findings were validated in cells and whole mouse embryos. Taken together, our study provides new evidence for a critical role of protein kinase CK2 in controlling DNA replication initiation and the expression levels of replicative DNA helicases, which ensure maintenance of proliferative potential and genome integrity in eukaryotic cells.
NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells
Authors: Chamoun-Emanuelli Ana M. , Bryan Laura K. , Cohen Noah D. , Tetrault Taylor L. , Szule Joseph A. , Barhoumi Rola , Whitfield-Cargile Canaan M. 
Published: October 2019

AbstractSmall intestinal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remains an under-recognized clinical disorder. The incomplete understanding of the pathophysiology has hampered the development of prevention and treatment strategies leading to the high morbidity and mortality rates. NSAIDs are known to modulate macroautophagy, a process indispensable for intestinal homeostasis. Whether NSAIDs stimulate or repress macroautophagy and how this correlates with the clinical manifestations of NSAID enteropathy, however, remains unknown. The objectives of this study were to determine whether NSAIDs impaired macroautophagy and how this affects macroautophagy-regulated intestinal epithelial cell (IEC) processes essential for intestinal homeostasis (i.e., clearance of invading pathogens, secretion and composition of mucus building blocks, and inflammatory response). We show that NSAID treatment of IECs inhibits macroautophagy in vitro and in vivo. This inhibition was likely attributed to a reduction in the area and/or distribution of lysosomes available for degradation of macroautophagy-targeted cargo. Importantly, IEC regulatory processes necessary for intestinal homeostasis and dependent on macroautophagy were dysfunctional in the presence of NSAIDs. Since macroautophagy is essential for gastrointestinal health, NSAID-induced inhibition of macroautophagy might contribute to the severity of intestinal injury by compromising the integrity of the mucosal barrier, preventing the clearance of invading microbes, and exacerbating the inflammatory response.
The interplay between chondrocyte spheroids and mesenchymal stem cells boosts cartilage regeneration within a 3D natural-based hydrogel
Authors: Scalzone Annachiara , Ferreira Ana M. , Tonda-Turo Chiara , Ciardelli Gianluca , Dalgarno Kenny , Gentile Piergiorgio 
Published: October 2019

AbstractArticular cartilage (AC) lacks the ability to self-repair and cell-based approaches, primarily based on using chondrocytes and mesenchymal stem cells (MSCs), are emerging as effective technology to restore cartilage functionality, because cells synergic functionality may support the maintenance of chondrogenic phenotype and promote extracellular matrix regeneration. This work aims to develop a more physiologically representative co-culture system to investigate the influence of MSCs on the activity of chondrocytes. A thermo-sensitive chitosan-based hydrogel, ionically crosslinked with β–glycerophosphate, is optimised to obtain sol/gel transition at physiological conditions within 5 minutes, high porosity with pores diameter <30 µm, and in vitro mechanical integrity with compressive and equilibrium Young’s moduli of 37 kPa and 17 kPa, respectively. Live/dead staining showed that after 1 and 3 days in culture, the encapsulated MSCs into the hydrogels are viable and characterised by round-like morphology. Furthermore chondrocyte spheroids, seeded on top of gels that contained either MSCs or no cells, show that the encapsulated MSCs stimulate chondrocyte activity within a gel co-culture, both in terms of maintaining the coherence of chondrocyte spheroids, leading to a larger quantity of CD44 (by immunofluorescence) and a higher production of collagen and glycosaminoglycans (by histology) compared with the mono-culture.
Altered metabolic gene expression in the brain of a triprolyl-human amylin transgenic mouse model of type 2 diabetes
Authors: Nie Tina , Zhang Shaoping , Vazhoor Amarsingh Greeshma , Liu Hong , McCann Mark J. , Cooper Garth J. S. 
Published: October 2019

AbstractType 2 diabetes mellitus is a major health concern worldwide; however, the molecular mechanism underlying its development is poorly understood. The hormone amylin is postulated to be involved, as human amylin forms amyloid in the pancreases of diabetic patients, and oligomers have been shown to be cytotoxic to β-cells. As rodent amylin is non-amyloidogenic, mice expressing human amylin have been developed to investigate this hypothesis. However, it is not possible to differentiate the effects of amylin overexpression from β-cell loss in these models. We have developed transgenic mice that overexpress [25, 28, 29 triprolyl]human amylin, a non-amyloidogenic variant of amylin, designated the Line 44 model. This model allows us to investigate the effects of chronic overexpression of non-cytotoxic amylin. We characterised this model and found it developed obesity, hyperglycaemia and hyperinsulinaemia. This phenotype was associated with alterations in the expression of genes involved in the amylin, insulin and leptin signalling pathways within the brain. This included genes such as c-Fos (a marker of amylin activation); Socs3 (a leptin inhibitor); and Cart, Pomc and Npy (neuropeptides that control appetite). We also examined Socs3 protein expression and phosphorylated Stat3 to determine if changes at the mRNA level would be reflected at the protein level.
Sensitivities to global change drivers may correlate positively or negatively in a foundational marine macroalga
Authors: Al-Janabi Balsam , Wahl Martin , Karsten Ulf , Graiff Angelika , Kruse Inken 
Published: October 2019

AbstractEcological impact of global change is generated by multiple synchronous or asynchronous drivers which interact with each other and with intraspecific variability of sensitivities. In three near-natural experiments, we explored response correlations of full-sibling germling families of the seaweed Fucus vesiculosus towards four global change drivers: elevated CO2 (ocean acidification, OA), ocean warming (OW), combined OA and warming (OAW), nutrient enrichment and hypoxic upwelling. Among families, performance responses to OA and OW as well as to OAW and nutrient enrichment correlated positively whereas performance responses to OAW and hypoxia anti-correlated. This indicates (i) that families robust to one of the three drivers (OA, OW, nutrients) will also not suffer from the two other shifts, and vice versa and (ii) families benefitting from OAW will more easily succumb to hypoxia. Our results may imply that selection under either OA, OW or eutrophication would enhance performance under the other two drivers but simultaneously render the population more susceptible to hypoxia. We conclude that intraspecific response correlations have a high potential to boost or hinder adaptation to multifactorial global change scenarios.
Modelling bacterial twitching in fluid flows: a CFD-DEM approach
Authors: Jayathilake Pahala Gedara , Li Bowen , Zuliani Paolo , Curtis Tom , Chen Jinju 
Published: October 2019

AbstractBacterial habitats are often associated with fluid flow environments. Bacterial twitching is important for initial bacterial colonization and biofilm formation. The existing research about bacteria twitching is largely experimental orientated. There is a lack of models of twitching motility of bacteria in shear flows, which could provide fundamental understanding about how bacterial twitching would be affected by bacteria associated properties such as number of pili and their distribution on the cell body and environmental factors such as flow and surface patterns. In this work, a three-dimensional modelling approach of Computational Fluid Dynamics (CFD) coupled with the Discrete Element Method (DEM) proposed to study bacterial twitching on flat and groove surfaces under shear flow conditions. Rod-shaped bacteria are modelled as groups of spherical particles and Type IV pili attached to bacteria are modelled as dynamic springs which can elongate, retract, attach and detach. The CFD-DEM model of rod-shape bacteria is validated against orbiting of immotile bacteria in shear flows. The effects of fluid flow rate and surface topography on twitching motility are studied. The model can successfully predict upstream twitching motility of rod-shaped bacteria in shear flows. Our model can predict that there would be an optimal range of wall shear stress in which bacterial upstream twitching is most efficient. The results also indicate that when bacteria twitch on groove surfaces, they are likely to accumulate around the downstream side of the groove walls.
Characterization of the FMDV-serotype-O isolates collected during 1962 and 1997 discloses new topotypes, CEY-1 and WCSA-1, and six new lineages
Authors: Ranaweera Lahiru Thilanka , Wijesundara Upendra Kumari , Jayarathne Hashan Sri-Madhubashana , Knowles Nick , Wadsworth Jemma , Mioulet Valerie , Adikari Jayantha , Weebadde Cholani , Sooriyapathirana Suneth S. 
Published: October 2019

AbstractThe genetic diversity of the FMD viruses collected from the outbreaks during the second half of the 20th Century in Sri Lanka was assessed in the present study. We sequenced the VP1 genomic region of the samples collected during FMDV epidemics caused by serotype O in Sri Lanka during 1962 and 1997. For comparison, we sequenced the VP1 of the related viral isolates collected from other Asian countries. We analyzed the VP1 sequences of the viral strains using the UPGMA method with uncorrected pairwise distances. Nucleotide divergence (ND) thresholds of 15%–20% and 5%–<15% were used to differentiate topotypes and lineages, respectively. We calibrated the divergence times and lineage-specific substitution rates using Bayesian-skyline models. Based on the ND estimations and phylogenetic relationships, we identified and named two new topotypes [CEYLON 1 (CEY-1) and WEST, CENTRAL AND SOUTH ASIA 1 (WCSA-1)] and six new lineages (Syr-62, Srl-77, Tur-69, May-78, Tai-87 and Bur-77) of serotype O. We believe that the novel topotypes and lineages named may have disappeared although they have similar substitution rates for epizootic outbreaks. Because the amino acid selection analysis revealed that the two topotypes and six lineages identified were under purifying selection during the outbreaks.
The age distribution of facial metrics in two large Korean populations
Authors: Lee Hae-Young , Cha Seongwon , Ban Hyo-Jeong , Kim In-Young , Park Bo-Reum , Kim Ig-Jae , Hong Kyung-Won 
Published: October 2019

AbstractGrowth and alterations in craniofacial morphology have attracted interest in many fields of science, especially physical anthropology, genetics and forensic sciences. We performed an analysis of craniofacial morphology alterations by gender and ageing stage in Korean populations. We studied 15 facial metrics using two large Korean populations (1,926 samples from the Korea Medicine Data Center cohort and 5,643 samples from the Ansan-Ansung cohort). Among the 15 metrics, 12 showed gender differences and tended to change with age. In both of the independent populations, brow ridge height, upper lip height, nasal tip height, and profile nasal length tended to increase with age, whereas outer canthal width, right palpebral fissure height, left palpebral fissure height, right upper lip thickness, left upper lip thickness, nasal tip protrusion, facial base width, and lower facial width tended to decrease. In conclusion, our findings suggest that ageing (past 40 years of age) might affect eye size, nose length, upper lip thickness, and facial width, possibly due to loss of elasticity in the face. Therefore, these facial metric changes could be applied to individual age prediction and aesthetic facial care.
Accuracy and performance of a new handheld ultrasound machine with wireless system
Authors: Zardi Enrico Maria , Franceschetti Edoardo , Giorgi Chiara , Palumbo Alessio , Franceschi Francesco 
Published: October 2019

AbstractWe verified the accuracy and performance of a new handheld ultrasound machine, in comparison to a high-end sonographic machine. We performed bilateral measurements of the following tendon districts (supraspinatus, flexor of the middle finger, patellar and Achilles) and of the cross sectional area of the median nerve in 21 patients using a musculoskeletal ultrasound linear scanner of a handheld sonographic machine and a high-end sonographic machine. Two tail T test was used to evaluate whether there were differences in the measurements between the two sonographic machines. Agreement was evaluated by Pearson’s correlation. The mean time requested for the examinations was 18 and 9 minutes for the handheld and high-end sonographic machines, respectively. No significant differences were found between the measurements obtained with the handheld ultrasound machine and those with the high-end sonographic machine (p value ranging between 0.31 and 0.97, according to the examined district), whereas, a moderate correlation was found (r coefficient ranging between 0.43 and 0.77, according to the examined district). Although the examination with the handheld ultrasound machine took more time, it showed adequate accuracy and performance; this palmar tool might be also useful in operating rooms.
Prognostic Value of Right Ventricular Dysfunction and Tricuspid Regurgitation in Patients with Severe Low-Flow Low-Gradient Aortic Stenosis
Authors: Zilberszac Robert , Gleiss Andreas , Schweitzer Ronny , Bruno Piergiorgio , Andreas Martin , Stelzmüller Marlies , Massetti Massimo , Wisser Wilfried , Laufer Günther , Binder Thomas , Gabriel Harald , Rosenhek Raphael 
Published: October 2019

AbstractLong and mid-term data in Low-Flow Low-Gradient Aortic Stenosis (LFLG-AS) are scarce. The present study sought to identify predictors of outcome in a sizeable cohort of patients with LFLG-AS. 76 consecutive patients with LFLG-AS (defined by a mean gradient <40 mmHg, an aortic valve area ≤1 cm2 and an ejection fraction ≤50%) were prospectively enrolled and followed at regular intervals. Events defined as aortic valve replacement (AVR) and death were assessed and overall survival was determined. 44 patients underwent AVR (10 transcatheter and 34 surgical) whilst intervention was not performed in 32 patients, including 9 patients that died during a median waiting time of 4 months. Survival was significantly better after AVR with survival rates of 91.8% (CI 71.1–97.9%), 83.0% (CI 60.7–93.3%) and 56.3% (CI 32.1–74.8%) at 1,2 and 5 years as compared to 84.3% (CI 66.2–93.1%), 52.9% (CI 33.7–69.0%) and 30.3% (CI 14.6–47.5%), respectively, for patients managed conservatively (p = 0.017). The presence of right ventricular dysfunction (HR 3.47 [1.70–7.09]) and significant tricuspid regurgitation (TR) (HR 2.23 [1.13–4.39]) independently predicted overall mortality while the presence of significant TR (HR 3.40[1.38–8.35]) and higher aortic jet velocity (HR 0.91[0.82–1.00]) were independent predictors of mortality and survival after AVR. AVR is associated with improved long-term survival in patients with LFLG-AS. Treatment delays are associated with excessive mortality, warranting urgent treatment in eligible patients. Right ventricular involvement characterized by the presence of TR and/or right ventricular dysfunction, identifies patients at high risk of mortality under both conservative management and after AVR.
Hepatospecific ablation of p38α MAPK governs liver regeneration through modulation of inflammatory response to CCl4-induced acute injury
Authors: Fortier Manon , Cadoux Mathilde , Boussetta Nadia , Pham Sandrine , Donné Romain , Couty Jean-Pierre , Desdouets Chantal , Celton-Morizur Séverine 
Published: October 2019

AbstractMammalian p38α MAPK (Mitogen-Activated Protein Kinase) transduces a variety of extracellular signals that regulate cellular processes, such as inflammation, differentiation, proliferation or apoptosis. In the liver, depending of the physiopathological context, p38α acts as a negative regulator of hepatocyte proliferation as well as a promotor of inflammatory processes. However, its function during an acute injury, in adult liver, remains uncharacterized. In this study, using mice that are deficient in p38α specifically in mature hepatocytes, we unexpectedly found that lack of p38α protected against acute injury induced by CCl4 compound. We demonstrated that the hepatoprotective effect alleviated ROS accumulation and shaped the inflammatory response to promote efficient tissue repair. Mechanistically, we provided strong evidence that Ccl2/Ccl5 chemokines were crucial for a proper hepatoprotective response observed secondary to p38α ablation. Indeed, antibody blockade of Ccl2/Ccl5 was sufficient to abrogate hepatoprotection through a concomitant decrease of both inflammatory cells recruitment and antioxidative response that result ultimately in higher liver damages. Our findings suggest that targeting p38α expression and consequently orientating immune response may represent an attractive approach to favor tissue recovery after acute liver injury.
Molecular recognition of ubiquitin and Lys63-linked diubiquitin by STAM2 UIM-SH3 dual domain: the effect of its linker length and flexibility
Authors: Nguyen Minh-Ha , Martin Marie , Kim Henry , Gabel Frank , Walker Olivier , Hologne Maggy 
Published: October 2019

AbstractMultidomain proteins represent a broad spectrum of the protein landscape and are involved in various interactions. They could be considered as modular building blocks assembled in distinct fashion and connected by linkers of varying lengths and sequences. Due to their intrinsic flexibility, these linkers provide proteins a subtle way to modulate interactions and explore a wide range of conformational space. In the present study, we are seeking to understand the effect of the flexibility and dynamics of the linker involved in the STAM2 UIM-SH3 dual domain protein with respect to molecular recognition. We have engineered several constructs of UIM-SH3 with different length linkers or domain deletion. By means of SAXS and NMR experiments, we have shown that the modification of the linker modifies the flexibility and the dynamics of UIM-SH3. Indeed, the global tumbling of both the UIM and SH3 domain is different but not independent from each other while the length of the linker has an impact on the ps-ns time scale dynamics of the respective domains. Finally, the modification of the flexibility and dynamics of the linker has a drastic effect on the interaction of UIM-SH3 with Lys63-linked diubiquitin with a roughly eight-time weaker dissociation constant.
Temporal and Spatial Expression of Arabidopsis Gene Homologs Control Daylength Adaptation and Bulb Formation in Onion (Allium cepa L.)
Authors: Rashid Md. Harun Ar , Cheng Wei , Thomas Brian 
Published: October 2019

AbstractGenetic studies aimed at onion improvement have been limited because of high heterozygosity, a very large genome size with a high level of repetitive DNA and a biennial life cycle. Onion bulb initiation is daylength-dependent, which places a significant barrier to adapting new varieties for growth at different latitudes. Compared to the photoperiodic regulation of flowering, relatively little is known about genetic regulation of the bulbing process. This study aims to identify the role of gene sequences involved in daylength-regulated bulb formation and tissue specific expression of onion. A comprehensive set of developmental and spatial quantitative mRNA expression experiments were carried out to investigate expression of onionFLOWERING LOCUS T(AcFT),LEAFY(AcLFY) andGIBBERELLIN-3 OXIDASE(GA3ox1) during the bulbing response. Bulbing ratios were used to measure the response of onion plants under long day (LD) and short day (SD) conditions.AcFT1was expressed in LD, which induces bulb formation, whileAcFT4was expressed in SD, which inhibits bulb formation.AcFT5andAcFT6were expressed in LD and might also be involved in bulb formation itself. AllAcFT, AcLFYandGA3ox1genes showed distinctive patterns of tissue specific expression in onion, withAcFTgenes found primarily in the sites of perception in the leaf and LFY in the basal tissues, the site of response. The results are consistent withAcFT1expression being the signal for LD-induced bulb initiation andAcFT4, being involved in suppressing bulbing in SD.
Pre-operative Localisation of the Parathyroid Glands in Secondary Hyperparathyroidism: A Retrospective Cohort Study
Authors: Hiramitsu Takahisa , Tomosugi Toshihide , Okada Manabu , Futamura Kenta , Tsujita Makoto , Goto Norihiko , Narumi Shunji , Watarai Yoshihiko , Tominaga Yoshihiro , Ichimori Toshihiro 
Published: October 2019

AbstractComplete parathyroidectomy (PTx) is essential during total PTx for secondary hyperparathyroidism (SHPT) to prevent recurrent and persistent hyperparathyroidism. Pre-operative imaging evaluations, including computed tomography (CT), ultrasonography (US), and Tc-99m sestamibi (MIBI) scans, are commonly performed. Between June 2009 and January 2016, 291 patients underwent PTx for SHPT after pre-operative evaluations involving CT, US, and MIBI scans, and the diagnostic accuracies of these imaging modalities for identifying the parathyroid glands were evaluated in 177 patients whose intact parathyroid hormone (PTH) levels were <9 pg/mL after the initial PTx. Additional PTx procedures were performed on 7 of 114 patients whose intact PTH levels were >9 ng/mL after PTx, and the diagnostic validities of the imaging modalities for the remnant parathyroid glands were evaluated. A combination of CT, US, and MIBI scans achieved the highest diagnostic accuracy (75%) for locating bilateral upper and lower parathyroid glands before initial PTx. The accuracies of CT, US, and MIBI scans with respect to locating remnant parathyroid glands before additional PTx were 100%, 28.6%, and 100%, respectively. A combination of CT, US, and MIBI scans is useful for initial PTx for SHPT, and CT and MIBI scans are useful imaging modalities for additional PTx procedures.