bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models
Authors: Marinello Martina , Werner Andreas , Giannone Mariagiovanna , Tahiri Khadija , Alves Sandro , Tesson Christelle , den Dunnen Wilfred , Seeler Jacob-S. , Brice Alexis , Sittler Annie 
Published: December 2018

ABSTRACT
Perturbation of protein homeostasis and aggregation of misfolded proteins is a major cause of many human diseases. A hallmark of the neurodegenerative disease spinocerebellar ataxia type 7 (SCA7) is the intranuclear accumulation of mutant, misfolded ataxin-7 (polyQ-ATXN7). Here, we show that endogenous ATXN7 is modified by SUMO proteins, thus also suggesting a physiological role for this modification under conditions of proteotoxic stress caused by the accumulation of polyQ-ATXN7. Co-immunoprecipitation experiments, immunofluorescence microscopy and proximity ligation assays confirmed the colocalization and interaction of polyQ-ATXN7 with SUMO2 in cells. Moreover, upon inhibition of the proteasome, both endogenous SUMO2/3 and the RNF4 ubiquitin ligase surround large polyQ-ATXN7 intranuclear inclusions. Overexpression of RNF4 and/or SUMO2 significantly decreased levels of polyQ-ATXN7 and, upon proteasomal inhibition, led to a marked increase in the polyubiquitination of polyQ-ATXN7. This provides a mechanism for the clearance of polyQ-ATXN7 from affected cells that involves the recruitment of RNF4 by SUMO2/3-modified polyQ-ATXN7, thus leading to its ubiquitination and proteasomal degradation. In a SCA7 knock-in mouse model, we similarly observed colocalization of SUMO2/3 with polyQ-ATXN7 inclusions in the cerebellum and retina. Furthermore, we detected accumulation of SUMO2/3 high-molecular-mass species in the cerebellum of SCA7 knock-in mice, compared with their wild-type littermates, and changes in SUMO-related transcripts. Immunohistochemical analysis showed the accumulation of SUMO proteins and RNF4 in the cerebellum of SCA7 patients. Taken together, our results show that the SUMO pathway contributes to the clearance of aggregated ATXN7 and suggest that its deregulation might be associated with SCA7 disease progression.
The Drosophila Dbf4 ortholog Chiffon forms a complex with Gcn5 that is necessary for histone acetylation and viability
Authors: Torres-Zelada Eliana F. , Stephenson Robert E. , Alpsoy Aktan , Anderson Benjamin D. , Swanson Selene K. , Florens Laurence , Dykhuizen Emily C. , Washburn Michael P. , Weake Vikki M. 
Published: December 2018

ABSTRACT
Metazoans contain two homologs of the Gcn5-binding protein Ada2, Ada2a and Ada2b, which nucleate formation of the ATAC and SAGA complexes, respectively. In Drosophila melanogaster, there are two splice isoforms of Ada2b: Ada2b-PA and Ada2b-PB. Here, we show that only the Ada2b-PB isoform is in SAGA; in contrast, Ada2b-PA associates with Gcn5, Ada3, Sgf29 and Chiffon, forming the Chiffon histone acetyltransferase (CHAT) complex. Chiffon is the Drosophila ortholog of Dbf4, which binds and activates the cell cycle kinase Cdc7 to initiate DNA replication. In flies, Chiffon and Cdc7 are required in ovary follicle cells for gene amplification, a specialized form of DNA re-replication. Although chiffon was previously reported to be dispensable for viability, here, we find that Chiffon is required for both histone acetylation and viability in flies. Surprisingly, we show that chiffon is a dicistronic gene that encodes distinct Cdc7- and CHAT-binding polypeptides. Although the Cdc7-binding domain of Chiffon is not required for viability in flies, the CHAT-binding domain is essential for viability, but is not required for gene amplification, arguing against a role in DNA replication.
ADAR2-mediated Q/R editing of GluK2 regulates kainate receptor upscaling in response to suppression of synaptic activity
Authors: Gurung Sonam , Evans Ashley J. , Wilkinson Kevin A. , Henley Jeremy M. 
Published: December 2018

ABSTRACT
Kainate receptors (KARs) regulate neuronal excitability and network function. Most KARs contain the subunit GluK2 (also known as GRIK2), and the properties of these receptors are determined in part by ADAR2 (also known as ADARB1)-mediated mRNA editing of GluK2, which changes a genomically encoded glutamine residue into an arginine residue (Q/R editing). Suppression of synaptic activity reduces ADAR2-dependent Q/R editing of GluK2 with a consequential increase in GluK2-containing KAR surface expression. However, the mechanism underlying this reduction in GluK2 editing has not been addressed. Here, we show that induction of KAR upscaling, a phenomenon in which surface expression of receptors is increased in response to a chronic decrease in synaptic activity, results in proteasomal degradation of ADAR2, which reduces GluK2 Q/R editing. Because KARs incorporating unedited GluK2(Q) assemble and exit the ER more efficiently, this leads to an upscaling of KAR surface expression. Consistent with this, we demonstrate that partial ADAR2 knockdown phenocopies and occludes KAR upscaling. Moreover, we show that although the AMPA receptor (AMPAR) subunit GluA2 (also known as GRIA2) also undergoes ADAR2-dependent Q/R editing, this process does not mediate AMPAR upscaling. These data demonstrate that activity-dependent regulation of ADAR2 proteostasis and GluK2 Q/R editing are key determinants of KAR, but not AMPAR, trafficking and upscaling.
This article has an associated First Person interview with the first author of the paper.
Nucleocytoplasmic distribution of S6K1 depends on the density and motility of MCF-7 cells in vitro
Authors: Kosach Viktoriia , Shkarina Kateryna , Kravchenko Anastasiia , Tereshchenko Yuliia , Kovalchuk Evelina , Skoroda Larysa , Krotevych Mykhailo , Khoruzhenko Antonina 
Published: December 2018

Background:The ribosomal protein S6 kinase 1 (S6K1) is one of the main components of the mTOR/S6K signal transduction pathway, which controls cellular metabolism, autophagy, growth, and proliferation. Overexpression of S6K1 was detected in tumors of different origin including breast cancer, and correlated with the worse disease outcome. In addition, significant accumulation of S6K1 was found in the nuclei of breast carcinoma cells suggesting the implication of kinase nuclear substrates in tumor progression. However, this aspect of S6K1 functioning is still poorly understood. The main aim of the present work was to study the subcellular localization of S6K1 in breast cancer cells with the focus on cell migration.Methods:Multicellular spheroids of MCF-7 cells were generated using agarose-coated Petri dishes. Cell migration was induced by spheroids seeding onto adhesive growth surface and subsequent cultivation for 24 to 72 hours. The subcellular localization of S6K1 was studied in human normal breast and cancer tissue samples, 2D and 3D MCF-7 cell cultures using immunofluorescence analysis and confocal microscopy.Results:Analysis of histological sections of human breast tissue samples revealed predominantly nuclear localization of S6K1 in breast malignant cells and its mainly cytoplasmic localization in conditionally normal cells.In vitrostudies of MCF-7 cells demonstrated that the subcellular localization of S6K1 depends on the cell density in the monolayer culture. S6K1 relocalization from the cytoplasm into the nucleus was detected in MCF-7 cells migrating from multicellular spheroids onto growth surface. Immunofluorescence analysis of S6K1 and immunocoprecipitation assay revealed the colocalization and interaction between S6K1 and transcription factor TBR2 (T-box brain protein 2) in MCF-7 cells.Conclusions:Subcellular localization of S6K1 depends on the density and locomotor activity of the MCF-7 cells.
Cortical auditory evoked potentials and hemispheric specialization of speech in individuals with learning disability and healthy controls: A preliminary study
Authors: Bhat Mayur , Palaniswamy Hari Prakash , Pichaimuthu Arivudai Nambi , Thomas Nitha 
Published: December 2018

Background: Dichotic listening (DL) technique is a behavioral non-invasive tool which is used in studying hemispheric lateralization. Previous studies using behavioral DL have hypothesized that individuals with learning disabilities (LD) exhibit a lack of cortical specialization for processing speech stimulus. However, there is no event related potential (ERP) evidence, hence the main objective of the study is to explore hemispheric asymmetry using cortical auditory evoked potential (CAEPs) in normal hearing adults and also to compare the same in children with LD and healthy controls. Methods: CAEPs were recorded in 16 normal hearing young adults, eight right-handed children with LD and their age matched controls. Two stop constants (/Pa/ – voiceless, bilabial, stop: /Ta/ - voiceless, alveolar, stop) were chosen for this experiment and presented in each ear and dichotically in two different orders (/pa-ta/, /ta-pa/). ERPs were processed using a standard pipeline, and electrodes readings over the left and right hemispheres were averaged to create left and right regions of interest (ROI). The CAEPs were analyzed for mean amplitude and peak latency of P1-N1-P2 components. Results: The current study results suggest no statistically significant difference between the two stimulus in monaural condition and absence of order effect in dichotic condition. In healthy controls the CAEP latencies were shorter over the left hemisphere in both monaural and dichotic conditions in adults and control children. However, it was very evident that such a difference was lacking in children with LD. Conclusions: Hemispheric asymmetry can be detected using CAEPs for speech stimulus. The measures are consistent and void of stimulus or order effect. Taken together, the findings of current study, both monaural and dichotic condition illustrates the hemispheric differences in processing speech stimuli in normal hearers. Absence of latency differences between hemispheres in children with LD indicate a lack of hemispheric asymmetry.
Diabetic foot ulcer treatment with focused shockwave therapy: two multicentre, prospective, controlled, double-blinded, randomised phase III clinical trials
Authors: Snyder Robert , Galiano Robert , Mayer Perry , Rogers Lee C. , Alvarez Oscar ,   The Sanuwave Trial Investigators
Published: December 2018

Objective: To investigate the efficacy of focused extracorporeal shockwave therapy (ESWT) as an adjunctive treatment for neuropathic diabetic foot ulcers (DFU) (1A or 2A on the University of Texas grading scheme), compared with sham treatment. Method: We performed two multicentre, randomised, sham-controlled, double-blinded, phase III clinical trials using focused ESWT compared with sham examining DFUs that did not reduce in volume by ≥50% over 2 weeks' standard treatment immediately prior to randomisation. Patients were enrolled into the trials and randomised for either standard care and focused ESWT (pulsed acoustic cellular expression. dermaPACE System, SANUWAVE Health Inc.) active therapy, or standard care and sham therapy. Both active and sham therapy were administered four times in 2 weeks in study 1 and a maximum of eight times over 12 weeks in study 2. Standard care continued in both studies throughout the 12-week treatment phase. The proportion of DFUs that closed completely by 12, 20 and 24 weeks was measured. Results: The two studies evaluated 336 patients; 172 patients treated with active therapy and 164 managed with a sham device. The demographic characteristics of patients in the two arms of both studies were balanced and statistical comparison of the two studies justified pooling datasets for analysis. Statistically significantly more DFU healed at 20 (35.5% versus 24.4%; p=0.027) and 24 weeks (37.8% versus 26.2%; p=0.023) in the active treatment arm compared with the sham-controlled arm. At 12 weeks the active therapy arm trended to significance (22.7% versus 18.3%). Conclusion: The outcome of these two trials suggests that ESWT is an effective therapeutic modality in combination with standard care for neuropathic DFU that do not respond to standard care alone.
Investigation of galectin-3 levels in diabetic foot ulcers
Authors: Gunes Ali Erdal , Eren Mehmet Ali , Koyuncu Ismail , Taskin Abdullah , Sabuncu Tevfik 
Published: December 2018

Objective:It has been shown that galectin-3 (Gal-3) promotes angiogenesis and new vessel formation. Serum Gal-3 is a risk factor for vascular complications in type 2 diabetes. The aim of this study is to compare Gal-3 levels with a range of biochemical parameters.Method:A prospective study consisted of individuals as a control group (group 1), patients diagnosed with type 2 diabetes without DFUs (group 2), and patients with type 2 diabetes with a DFU (group 3). Patient levels of endothelin-1 (ET-1), vascular endothelial growth factor-A (VEGF-A), nitric oxide (NO), and Gal-3 were measured.Results:In total, 91 patients participated, (28 male, 63 female with a mean age of 55.83±6.35 years) Mean ET-1 (39.0±16.9), NO (17.6±7.6), VEGF-A (33.5±13.4) and Gal-3 (535.1±420.5) levels were significantly higher in group 3 compared with the other two groups (p<0.01). Furthermore, the Gal-3 level was positively and statistically significantly correlated with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ET-1 and NO levels in all groups.Conclusion:In our study, the level of Gal-3 was shown to be positively correlated with the VEGF-A level. Hence, Gal-3 can be considered as a defence mechanism against complications of diabetes, thus contributing to wound healing. Gal-3 may play a critical role in DFU formation and progression. Moreover, it could be suggested that Gal-3 may give an indication of prognosis, as it elevates VEGF-A levels and stimulates angiogenesis. Further studies are required to confirm the findings of this study.
Surgical site infections after craniotomy: a matched health-care cost and length of stay study
Authors: Hweidi Issa M. , Barbarawi Mohammed Al , Tawalbeh Loai Issa , Al-hassan Musa A. , Al-Ibraheem Saba W. 
Published: December 2018

Objective: To assess the extra health-care costs and length of stay resulting from surgical site infection (SSI), as well as to identify the most frequent aetiological microorganisms of SSIs among Jordanian craniotomy surgery patients. Method: A retrospective, descriptive, correlational and nested 1:1 matched case-control design was used. A computerised list of patients, who underwent surgery between May 2009 and March 2015, was generated in the targeted hospital. A final bill for every selected patient was also determined. Patients were divided equally into two groups: patients with an SSI and patients without an SSI. Results: A total of 64 patients were recruited. The SSI-group had a significant higher mean health-care cost of $7,899.08 (p=0.001) and a longer stay in hospital (mean additional days: 23.17) than the non-SSI group. Furthermore, Acinetobacter baumannii and Staphylococcus aureus were determined as the most predominant causative agents of SSI, at 39.1% and 26.1% of SSI patients, respectively. Conclusion: The results of this study can be considered as a baseline for national benchmarking to evaluate the quality of care provided to targeted patients. This study should encourage nurse administrators to adopt protocols and strategies that promote infection control measures, as well as to develop new methods of surveillance on universal precautions adherence. This may limit pathogen contamination in the surgical wound, shorten length of stay and decrease health-care costs.
Modern band: A descriptive study of teacher perceptions
Authors: Randles Clint 
Published: December 2018

Abstract
This study is a descriptive evaluation of the work of Little Kids Rock, a US non-profit organization that provided at the time of data collection free music instruction and instruments to over 187,754 students, 1120 teachers, in 30 cities around the United States. Music teachers (N=62 of 1120, 68% response rate) completed an end-of-the-year assessment of their perceptions of the learning outcomes of students involved with the programme. According to teachers’ perceptions: a majority of the programmes around the country utilize the acoustic guitar (94%), students have performed a few songs that they choose (66%), and students appear to be more engaged (76%) in their music classes. However, teachers believe that a majority of students have not composed an original song (68%), and cannot improvise on an instrument (68%). Implications for the future of the programme include better equipping teachers to teach songwriting and improvisation.
A 16-week multicenter observational study of the efficiency and safety of rheumatoid arthritis therapy with methotrexate
Authors: Balabanova R. M. 
Published: December 2018

Objective: to evaluate the efficiency of combination therapy with methotrexate (MTX) and hydroxychloroquine (HC) in rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The investigation enrolled 430 patients with documented RA who had been followed up for 16 weeks by rheumatologists in different regions of the country. Individual schedules were filled out for the patients, by adding demographic, clinical, and laboratory parameters that made it possible to assess the activity of the disease and to estimate the level of glucose, cholesterol, and low-density lipoproteins (LDL). The results of the investigation were evaluated at the inclusion of patients in it and then at 8 and 16 weeks. Taking into account the insufficient previous effect of MTX, the treatment was enhanced by HC.Results and discussion. By the end of the investigation, the combination therapy with MTX + HC led to significant decreases in the number of swollen and tender joints, the duration of morning stiffness, the severity of pain, and the integrated DAS28 index. The therapy showed a positive effect on the levels of fasting glucose, cholesterol, and LDL. The quality of life improved in patients by Visit 3. The results obtained are in good agreement with the data by foreign and Russian investigators on the greater efficiency of combination therapy with MTX + HC than that of MTX monotherapy and on the pleiotropic (hypolipidemic and hypolipidemic) effect of HC.Conclusion. It is concluded that in Russian practice when monotherapy with MTX shows an insufficient effect or its high doses cannot be administered to enhance the efficacy of RA therapy, it is possible to use a combination of MTX + HC, especially in older patients with comorbidity (hyperglycemia and hypercholesterolemia).
General principles in the treatment of lupus nephritis with the prevention of cardiovascular events
Authors: Panafidina Т. A. , Popkova Т. V. 
Published: December 2018

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology, which is characterized by the hyperproduction of organ-nonspecific autoantibodies to various components of the cell nucleus with the development of immunoinflammatory tissue and visceral damages. Kidney damage is one of the most common severe manifestations of SLE, which develops in 40–80% of patients and, in 15–20% of them, progresses to end-stage renal failure. A renal biopsy is recommended for all patients with lupus nephritis (LN) when choosing a successful treatment policy added by immunosuppressive therapy.The paper presents treatments for LN according to its morphological class with a dosage detailed description, a route of administration, and the duration of intake of different drug groups in the induction and maintenance phases of treatment, as well as the specific features of therapy for refractory LN. Taking into account that patients with SLE in general and those with LN in particular have an increased rate of cardiovascular events, the authors have proposed exposures to traditional and specific risk factors for cardiovascular diseases.
Facial agnosia in the clinical presentations of brain lesions
Authors: Grigoryeva V. N. , Mashkovich K. A. 
Published: December 2018

Facial agnosia (prosopagnosia) is one of the causes of limitations in the life of patients with focal vascular, inflammatory, traumatic, and tumor lesions of the brain; however, the clinical significance of these lesions in neurological practice is often underestimated.The review briefly presents the current understanding of the neurophysiological basis of facial gnosis and its neuroanatomic correlates. It discusses the clinical variants of prosopagnosia, the features of neuropsychological diagnosis, and adopted approaches to patient rehabilitation. It also highlights the importance of developing standardized methods for facial agnosia to improve the detection of prosopagnosia in focal brain lesions.
Impact of stimulating cognitive-motor training on neuropsychological status and quality of life in patients with Parkinson's disease
Authors: Bykov Yu. N. , Bender T. B. , Vasiliev Yu. N. , Kalyagin A. N. , Maksikova Т. М. , Orlova G. M. , Kozlova N. M. , Ryzhkova O. V. 
Published: December 2018

Motor and non-motor symptoms are identified in the clinical picture of Parkinson's disease (PD). Among its non-motor manifestations, cognitive impairment (CI) and emotional disorders play a special role in PD. It is important to search for new forms and methods of cognitive therapy in patients with PD.Objective:to analyze neuropsychological status and quality of life (QOL) in PD patients and to evaluate the efficiency of personalized combination therapy with a stimulating cognitive motor training on computer and mobile devices in these patients.Patients and methods. The investigation enrolled 112 patients with PD. A study group included 56 PD patients who received a cycle of combination therapy with cognitive-motor training on PC and mobile devices; a control group consisted of 56 PD patients who had only a drug therapy cycle. To evaluate neuropsychological status and QOL, the investigators used the Montreal Cognitive Assessment (MoCA), the McNair and Kahn memory self-evaluation scale, the Hospital Anxiety and Depression Scale (HADS), and the 36-Item Short Form Health Survey (SF-36) questionnaire.Results and discussion. According to MoCA scores, CI of varying severity was diagnosed in the majority of patients: in 75 and 80.4% in the study and control groups, respectively. Depressive syndrome was detected in 53.6 and 64.3% in these groups, respectively. According to the SF-36, the physical status of patients had the greatest effect in reducing their QOL. There were treatment-induced statistically significant positive changes for the following domains: physical functioning (p<0.01), role-physical functioning (p<0.001), pain intensity (p<0.01), general health (p<0.01), role emotional (p<0.0001), and mental health (p<0.01).Conclusion.The investigation has shown the efficiency of personalized therapy including stimulating cognitive-motor training on computer and mobile devices, which improves neuropsychological status and QOL in patients with PD.
Sampling and collecting foliage elements for the determination of the foliar nutrients in ICOS ecosystem stations
Authors: Loustau Denis , Altimir Nuria , Barbaste Mireille , Gielen Bert , Jiménez Sara Marańón , Klumpp Katja , Linder Sune , Matteucci Giorgio , Merbold Lutz , de Beek Marteen Op , Soulé Patrice , Thimonier Anne , Vincke Caroline , Waldner Peter 
Published: December 2018

Abstract
The nutritional status of plant canopies in terms of nutrients (C, N, P, K, Ca, Mg, Mn, Fe, Cu, Zn) exerts a strong influence on the carbon cycle and energy balance of terrestrial ecosystems. Therefore, in order to account for the spatial and temporal variations in nutritional status of the plant species composing the canopy, we detail the methodology applied to achieve consistent time-series of leaf mass to area ratio and nutrient content of the foliage within the footprint of the Integrated Carbon Observation System Ecosystem stations. The guidelines and defi-nitions apply to most terrestrial ecosystems.