bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse lesion and necrosis tied to poorer prognosis of interdigitating dendritic cell sarcoma: cases report and a pooled analysis
Authors: Shi Feng , Song Qingkun , Wang Lingling , Gao Ying , Chang Hong 
Published: March 2017

AbstractInterdigitating dendritic cell sarcoma is a neoplastic proliferation of interdigitating dendritic cells and no therapeutic consensus exists. This study aimed to investigate the prognostic impacts of tumor lesion, cellular atypia, mitosis and necrosis on the interdigitating dendritic cell sarcoma. Case reports and pooled analyses were designed to explore the relationships. One case was a 40-years old man with localized lesion, moderate to notable cellular atypia, 30 mitoses per 10 high-power fields and no necrosis and the progression-free survival was longer than 20 months. The other case was a 62-years old woman with diffuse lesion, notable cellular atypia, less than one mitosis per 10 high-power fields and diffuse necrosis and the progression-free survival was shorter than 1 month. Cellular atypia and mitosis had not any relationship with survival. Compared with localized lesion, diffuse lesion presented a 2.92-fold risk of progression (HR = 2.92, 95% CI 1.01, 8.51) and an 8.79-fold risk of death (HR = 8.79, 95% CI 1.86, 41.64). Diffuse necrosis presented a 4.39-fold higher progression risk (HR = 5.39, 95% CI 1.78, 16.29) and a 5.37-fold higher death risk (HR = 6.37, 95% CI 1.46, 27.86) than focal or no necrosis. Diffuse lesion and diffuse necrosis were indicators of poorer prognosis and the clinical application should be warranted in further studies.
Computer vision distortion correction of scanning probe microscopy images
Authors: Gaponenko Iaroslav , Tückmantel Philippe , Ziegler Benedikt , Rapin Guillaume , Chhikara Manisha , Paruch Patrycja 
Published: March 2017

AbstractSince its inception, scanning probe microscopy (SPM) has established itself as the tool of choice for probing surfaces and functionalities at the nanoscale. Although recent developments in the instrumentation have greatly improved the metrological aspects of SPM, it is still plagued by the drifts and nonlinearities of the piezoelectric actuators underlying the precise nanoscale motion. In this work, we present an innovative computer-vision-based distortion correction algorithm for offline processing of functional SPM measurements, allowing two images to be directly overlaid with minimal error – thus correlating position with time evolution and local functionality. To demonstrate its versatility, the algorithm is applied to two very different systems. First, we show the tracking of polarisation switching in an epitaxial Pb(Zr0.2Ti0.8)O3 thin film during high-speed continuous scanning under applied tip bias. Thanks to the precise time-location-polarisation correlation we can extract the regions of domain nucleation and track the motion of domain walls until the merging of the latter in avalanche-like events. Secondly, the morphology of surface folds and wrinkles in graphene deposited on a PET substrate is probed as a function of applied strain, allowing the relaxation of individual wrinkles to be tracked.
Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina
Authors: Olivares A. M. , Jelcick A. S. , Reinecke J. , Leehy B. , Haider A. , Morrison M. A. , Cheng L. , Chen D. F. , DeAngelis M. M. , Haider N. B. 
Published: March 2017

AbstractRegulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.
Neuronal p38α mediates synaptic and cognitive dysfunction in an Alzheimer’s mouse model by controlling β-amyloid production
Authors: Colié Sandra , Sarroca Sara , Palenzuela Rocío , Garcia Idoia , Matheu Ander , Corpas Rubén , Dotti Carlos G. , Esteban José A. , Sanfeliu Coral , Nebreda Angel R. 
Published: March 2017

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by a severe and progressive neuronal loss leading to cognitive dysfunctions. Previous reports, based on the use of chemical inhibitors, have connected the stress kinase p38α to neuroinflammation, neuronal death and synaptic dysfunction. To explore the specific role of neuronal p38α signalling in the appearance of pathological symptoms, we have generated mice that combine expression of the 5XFAD transgenes to induce AD symptoms with the downregulation of p38α only in neurons (5XFAD/p38α∆-N). We found that the neuronal-specific deletion of p38α improves the memory loss and long-term potentiation impairment induced by 5XFAD transgenes. Furthermore, 5XFAD/p38α∆-N mice display reduced amyloid-β accumulation, improved neurogenesis, and important changes in brain cytokine expression compared with 5XFAD mice. Our results implicate neuronal p38α signalling in the synaptic plasticity dysfunction and memory impairment observed in 5XFAD mice, by regulating both amyloid-β deposition in the brain and the relay of this accumulation to mount an inflammatory response, which leads to the cognitive deficits.
Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection
Authors: Wassmer Sarah J. , Carvalho Livia S. , György Bence , Vandenberghe Luk H. , Maguire Casey A. 
Published: March 2017

AbstractWidespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors. Vectors were IVT injected into the eyes of adult mice. GFP expression was noninvasively monitored by fundus imaging and retinal expression was analyzed 4 weeks post-injection by qRT-PCR and histology. Exo-AAV2 outperformed conventional AAV2 in GFP expression based on fundus image analysis and qRT-PCR. Exo-AAV2 demonstrated deeper penetration in the retina, efficiently reaching the inner nuclear and outer plexiform, and to a lesser extent the outer nuclear layer. Cell targets were ganglion cells, bipolar cells, Müller cells, and photoreceptors. Exo-AAV2 serves as a robust gene delivery tool for murine retina, and the simplicity of production and isolation should make it widely applicable to basic research of the eye.
A novel method for non-destructive determination of hair photo-induced damage based on multispectral imaging technology
Authors: Cao Yue , Qu Hao , Xiong Can , Liu Changhong , Zheng Lei 
Published: March 2017

AbstractExtended exposure to sunlight may give rise to chemical and physical damages of human hairs. In this work, we report a novel method for non-destructive quantification of hair photodamage via multispectral imaging (MSI) technology. We show that the multispectral reflectance value in near-infrared region has a strong correlation with hair photodamage. More specifically, the hair segments with longer growing time and the same hair root segment after continuous ultraviolet (UV) irradiation displaying more severe photodamage observed via scanning electron microscopy (SEM) micrographs showed significantly higher multispectral reflectance value. Besides, the multispectral reflectance value of hair segments with different growing time was precisely reproduced by exposing the same hair root segment to specific durations of UV irradiation, suggesting that MSI can be adequately applied to determine the sunlight exposure time of the hair. The loss of cystine content of photodamaged hairs was identified to be the main factor that physiologically contributed to the morphological changes of hair surface fibers and hence the variation of their multispectral reflectance spectra. Considering the environmental information recording nature of hairs, we believe that MSI for non-destructive evaluation of hair photodamage would prove valuable for assessing sunlight exposure time of a subject in the biomedical fields.
PCTK3/CDK18 regulates cell migration and adhesion by negatively modulating FAK activity
Authors: Matsuda Shinya , Kawamoto Kohei , Miyamoto Kenji , Tsuji Akihiko , Yuasa Keizo 
Published: March 2017

AbstractPCTAIRE kinase 3 (PCTK3) is a member of the cyclin dependent kinase family, but its physiological function remains unknown. We previously reported that PCTK3-knockdown HEK293T cells showed actin accumulation at the leading edge, suggesting that PCTK3 is involved in the regulation of actin reorganization. In this study, we investigated the physiological function and downstream signal transduction molecules of PCTK3. PCTK3 knockdown in HEK293T cells increased cell motility and RhoA/Rho-associated kinase activity as compared with control cells. We also found that phosphorylation at residue Tyr-397 in focal adhesion kinase (FAK) was increased in PCTK3-knockdown cells. FAK phosphorylation at Tyr-397 was increased in response to fibronectin stimulation, whereas its phosphorylation was suppressed by PCTK3. In addition, excessive expression of PCTK3 led to the formation of filopodia during the early stages of cell adhesion in HeLa cells. These results indicate that PCTK3 controls actin cytoskeleton dynamics by negatively regulating the FAK/Rho signaling pathway.
An Inter-comparison of Three Heat Wave Types in China during 1961–2010: Observed Basic Features and Linear Trends
Authors: Chen Yang , Li Yi 
Published: March 2017

AbstractUsing observed daily temperatures in China, three independent types of heat waves (HWs), including daytime HWs, nighttime HWs, and compound HWs (with both extreme daily maxima and minima), were defined. Different types of HWs showed distinctive preferences in occurrence locations and timing. However, spatial patterns of accompanying relative humidity were generally independent of categorization, except for closer association of nighttime events with high humidity level. Compound HWs and nighttime HWs experienced significant increases in frequency, participating days, mean duration, intensity and areal extent. Conversely, significant decreasing trends of above indicators prevailed in daytime HWs, especially in central-eastern China. Tendency of relative humidity changes didn’t vary with HW types. Instead it caused an interesting phenomenon that dry HWs in the west became more humid and humid events in the east got dryer, as manifested most obviously in compound type. Thorough comparisons highlight the evolutionary dominance of HW types. Specifically, previously-dominating independent daytime HWs have been increasingly replaced by independent nighttime events in central-eastern China, and by compound HWs in southern China. That’s the very reason for negative trends of independent daytime HWs in eastern China, even in a warming climate.
Microvascular vasodilator properties of the angiotensin II type 2 receptor in a mouse model of type 1 diabetes
Authors: Begorre Marc-Antoine , Dib Abdallah , Habchi Khalil , Guihot Anne-Laure , Bourreau Jennifer , Vessieres Emilie , Blondeau Bertrand , Loufrani Laurent , Chabbert Marie , Henrion Daniel , Fassot Céline 
Published: March 2017

AbstractDiabetes Mellitus is associated with severe cardiovascular disorders involving the renin-angiotensin system, mainly through activation of the angiotensin II type 1 receptor (AT1R). Although the type 2 receptor (AT2R) opposes the effects of AT1R, with vasodilator and anti-trophic properties, its role in diabetes is debatable. Thus we investigated AT2R-mediated dilatation in a model of type 1 diabetes induced by streptozotocin in 5-month-old male mice lacking AT2R (AT2R−/y). Glucose tolerance was reduced and markers of inflammation and oxidative stress (cyclooxygenase-2, gp91phox p22phox and p67phox) were increased in AT2R−/y mice compared to wild-type (WT) animals. Streptozotocin-induced hyperglycaemia was higher in AT2R−/y than in WT mice. Arterial gp91phox and MnSOD expression levels in addition to blood 8-isoprostane and creatinine were further increased in diabetic AT2R−/y mice compared to diabetic WT mice. AT2R-dependent dilatation in both isolated mesenteric resistance arteries and perfused kidneys was greater in diabetic mice than in non-diabetic animals. Thus, in type 1 diabetes, AT2R may reduce glycaemia and display anti-oxidant and/or anti-inflammatory properties in association with greater vasodilatation in mesenteric arteries and in the renal vasculature, a major target of diabetes. Therefore AT2R might represent a new therapeutic target in diabetes.
Endoscopic nipple sparing mastectomy with immediate implant-based reconstruction versus breast conserving surgery: a long-term study
Authors: Du Junze , Liang Quankun , Qi Xiaowei , Ming Jia , Liu Jing , Zhong Ling , Fan Linjun , Jiang Jun 
Published: March 2017

AbstractTo evaluate the differences between endoscopic nipple sparing mastectomy (ENSM) with immediate implant-based reconstruction and breast conserving surgery(BCS) applied to early-stage breast cancer in postoperative outcomes, function, and cosmesis. we made a prospective, non-randomized study reviewed a total of 346 cases of breast cancer from January 2007 to December 2011, including 189 cases of BCS and 157 cases of ENSM. All the patients were followed up to April 2016, with a median follow-up time of 74 months. The operative time, blood loss and drainage, postoperative complications, postoperative cosmesis, local recurrence rate, disease-free survival rate and overall survival rate of the two groups were compared. we found out that the operative time of ENSM was longer than that of BCS. There was no difference in blood loss and drainage, the postoperative complications, the disease-free survival rate and overall survival rate between the two groups. In regarding to cosmesis, patients in the ENSM group were more likely to get a satisfactory postoperative breast appearance. we reached a conclusion that ENSM is a safe and effective operative method retainingadvantages of TSSM to further improve the postoperative cosmetic effect, without increasing other risks. The surgery provides a new choice for patients with early-stage breast cancer.
Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types
Authors: Chen Ying-Jiun J. , Friedman Brad A. , Ha Connie , Durinck Steffen , Liu Jinfeng , Rubenstein John L. , Seshagiri Somasekar , Modrusan Zora 
Published: March 2017

AbstractMany subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified. A few non-neuronal cell types were detected, including microglia. In vitro MGE-like cells resembled bona fide MGE cells but expressed lower levels of Foxg1 and Epha4. Together, our data provide detailed understanding of the embryonic MGE developmental program and suggest how CINs are specified.
Discovery of the first dual GSK3β inhibitor/Nrf2 inducer. A new multitarget therapeutic strategy for Alzheimer’s disease
Authors: Gameiro Isabel , Michalska Patrycja , Tenti Giammarco , Cores Ángel , Buendia Izaskun , Rojo Ana I. , Georgakopoulos Nikolaos D. , Hernández-Guijo Jesús M. , Teresa Ramos María , Wells Geoffrey , López Manuela G. , Cuadrado Antonio , Menéndez J. Carlos , León Rafael 
Published: March 2017

AbstractThe formation of neurofibrillary tangles (NFTs), oxidative stress and neuroinflammation have emerged as key targets for the treatment of Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder. These pathological hallmarks are closely related to the over-activity of the enzyme GSK3β and the downregulation of the defense pathway Nrf2-EpRE observed in AD patients. Herein, we report the synthesis and pharmacological evaluation of a new family of multitarget 2,4-dihydropyrano[2,3-c]pyrazoles as dual GSK3β inhibitors and Nrf2 inducers. These compounds are able to inhibit GSK3β and induce the Nrf2 phase II antioxidant and anti-inflammatory pathway at micromolar concentrations, showing interesting structure-activity relationships. The association of both activities has resulted in a remarkable anti-inflammatory ability with an interesting neuroprotective profile on in vitro models of neuronal death induced by oxidative stress and energy depletion and AD. Furthermore, none of the compounds exhibited in vitro neurotoxicity or hepatotoxicity and hence they had improved safety profiles compared to the known electrophilic Nrf2 inducers. In conclusion, the combination of both activities in this family of multitarget compounds confers them a notable interest for the development of lead compounds for the treatment of AD.
Prion-like characteristics of the bacterial protein Microcin E492
Authors: Shahnawaz Mohammad , Park Kyung-Won , Mukherjee Abhisek , Diaz-Espinoza Rodrigo , Soto Claudio 
Published: March 2017

AbstractMicrocin E492 (Mcc) is a pore-forming bacteriotoxin. Mcc activity is inhibited at the stationary phase by formation of amyloid-like aggregates in the culture. Here we report that, in a similar manner as prions, Mcc naturally exists as two conformers: a β-sheet-rich, protease-resistant, aggregated, inactive form (Mccia), and a soluble, protease-sensitive, active form (Mcca). The exogenous addition of culture medium containing Mccia or purified in vitro-generated Mccia into the culture induces the rapid and efficient conversion of Mcca into Mccia, which is maintained indefinitely after passaging, changing the bacterial phenotype. Mccia prion-like activity is conformation-dependent and could be reduced by immunodepleting Mccia. Interestingly, an internal region of Mcc shares sequence similarity with the central domain of the prion protein, which is key to the formation of mammalian prions. A synthetic peptide spanning this sequence forms amyloid-like fibrils in vitro and is capable of inducing the conversion of Mcca into Mcciain vivo, suggesting that this region corresponds to the prion domain of Mcc. Our findings suggest that Mcc is the first prokaryotic protein with prion properties which harnesses prion-like transmission to regulate protein function, suggesting that propagation of biological information using a prion-based conformational switch is an evolutionary conserved mechanism.
Inhibitory Potential of Constituents from Osmanthus fragrans and Structural Analogues Against Advanced Glycation End Products, α-Amylase, α-Glucosidase, and Oxidative Stress
Authors: Yang Ji-Yeon , Park Jun-Hwan , Chung Namhyun , Lee Hoi-Seon 
Published: March 2017

AbstractInhibition of α-amylase and α-glucosidase, advanced glycation end products (AGEs) formation, and oxidative stress by isolated active constituents of Osmanthus fragrans flowers (9,12-octadecadienoic acid and 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one) and their structural analogues were evaluated. 9,12-Octadecadienoic acid was 10.02 and 22.21 times more active against α-amylase and α-glucosidase, respectively, than acarbose and ascorbic acid, followed by 9,12,15-octadecatrienoic acid, 9-octadecenoic acid, 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one, 4-(2,6,6-trimethyl-2-cyclohexenyl)-3-buten-2-one, 1-heptadecanecarboxylic acid, and 1-pentadecanecarboxylic acid. Concerning the inhibition of AGEs formation, similar with data for 2,2’-diphenyl-1-picrylhydrazl radical scavenging activities, 9,12-octadecadienoic acid was 3.54 times more active than aminoguanidine, followed by 9,12,15-octadecatrienoic acid, and 9-octadecenoic acid. These results indicate that 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one, 9,12-octadecadienoic acid and their analogues inhibit α-amylase and α-glucosidase, AGEs formation, and oxidative stress have potential value in alleviating diabetic pathological conditions.
Hidden Markov models reveal complexity in the diving behaviour of short-finned pilot whales
Authors: Quick Nicola J. , Isojunno Saana , Sadykova Dina , Bowers Matthew , Nowacek Douglas P. , Read Andrew J. 
Published: March 2017

AbstractDiving behaviour of short-finned pilot whales is often described by two states; deep foraging and shallow, non-foraging dives. However, this simple classification system ignores much of the variation that occurs during subsurface periods. We used multi-state hidden Markov models (HMM) to characterize states of diving behaviour and the transitions between states in short-finned pilot whales. We used three parameters (number of buzzes, maximum dive depth and duration) measured in 259 dives by digital acoustic recording tags (DTAGs) deployed on 20 individual whales off Cape Hatteras, North Carolina, USA. The HMM identified a four-state model as the best descriptor of diving behaviour. The state-dependent distributions for the diving parameters showed variation between states, indicative of different diving behaviours. Transition probabilities were considerably higher for state persistence than state switching, indicating that dive types occurred in bouts. Our results indicate that subsurface behaviour in short-finned pilot whales is more complex than a simple dichotomy of deep and shallow diving states, and labelling all subsurface behaviour as deep dives or shallow dives discounts a significant amount of important variation. We discuss potential drivers of these patterns, including variation in foraging success, prey availability and selection, bathymetry, physiological constraints and socially mediated behaviour.