bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of ALK7 inhibits high glucose‐induced oxidative stress and apoptosis in retinal pigment epithelial cells
Authors: Shi Qiang , Dong Xiaomin , Zhang Ming , Cheng Yuhong , Pei Cheng 
Published: October 2019

AbstractDiabetic retinopathy (DR) is one of the diabetic complications associated with hyperglycaemia‐mediated oxidative stress. Activin receptor‐like kinase 7 (ALK7) has been proven to be a potential therapeutic approach for diabetic cardiomyopathy, which is another diabetic complication. However, the role of ALK7 in DR remains unclear. In the current study, ALK7 was found to be up‐regulated in clinical samples from DR patients and high glucose (HG)‐induced human retinal pigment epithelial cells (ARPE‐19). In vitro studies demonstrated that knockdown of ALK7 in ARPE‐19 cells through transfection with siRNA‐ALK7 (si‐ALK7) improved cell viability in HG‐induced ARPE‐19 cells. Knockdown of ALK7 suppressed HG‐induced reactive oxygen species (ROS) production, as well elevating the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in ARPE‐19 cells. The number of apoptotic cells was significantly decreased after transfection with si‐ALK7. ALK7 knockdown also caused a significant decrease in bax expression and an increase in bcl‐2 expression in HG‐induced ARPE‐19 cells. In addition, ALK7 knockdown resulted in remarkable increase in the expressions of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and heme oxygenase‐1 (HO‐1) in ARPE‐19 cells in response to HG induction. Taken together, knockdown of ALK7 protected ARPE‐19 cells from HG‐induced oxidative injury, which might be mediated by the activation of the Nrf2/HO‐1 signalling pathway.
Persister cells resuscitate via ribosome modification by 23S rRNA pseudouridine synthase RluD
Authors: Song Sooyeon , Wood Thomas K. 
Published: October 2019

SummaryUpon a wide range of stress conditions (e.g. nutrient, antibiotic, oxidative), a subpopulation of bacterial cells known as persisters survives by halting metabolism. These cells resuscitate rapidly to reconstitute infections once the stress is removed and nutrients are provided. However, how these dormant cells resuscitate is not understood well but involves reactivating ribosomes. By screening 10,000 compounds directly for stimulating Escherichia coli persister cell resuscitation, we identified that 2‐{[2‐(4‐bromophenyl)‐2‐oxoethyl]thio}‐3‐ethyl‐5,6,7,8‐tetrahydro[1]benzothieno[2,3‐d]pyrimidin‐4(3H)‐one (BPOET) stimulates resuscitation. Critically, by screening 4267 E. coli proteins, we determined that BPOET activates hibernating ribosomes via 23S rRNA pseudouridine synthase RluD, which increases ribosome activity. Corroborating the increased waking with RluD, production of RluD increased the number of active ribosomes in persister cells. Also, inactivating the small RNA RybB which represses rluD led to faster persister resuscitation. Hence, persister cells resuscitate via activation of RluD.
Does working channel position influence the effectiveness of flexible ureteroscopy? Results from an in vitro study
Authors: Villa Luca , Ventimiglia Eugenio , Proietti Silvia , Giusti Guido , Briganti Alberto , Salonia Andrea , Montorsi Francesco , Doizi Steeve , Traxer Olivier 
Published: October 2019

AbstractObjectiveTo evaluate whether the position of the working channel affects the effectiveness of flexible ureteroscopy.Materials and MethodsWe compared the ureteroscopes Flex‐X2S and Flex‐XC (working channel at the 9 and 3 o’clock positions, respectively) in eight cavities of a K‐Box model, simulating the distribution of the right and left intrarenal calyces. In the first and second settings, each cavity contained a 1‐cm stone, lying on the bottom and fixed on the anterior sheet covering the box, respectively. In the third setting, the posterior and lateral surface of each cavity was draped with graph paper. Once the flexible ureteroscope entered each cavity, we measured and compared (i) the proportion of stone surface targeted by the laser (STL) and (ii) the proportion of graph paper burned by the laser (PBL) obtained with the two instruments.ResultsHigher STLs and PBLs were obtained with the 3 o’clock position than the 9 o’clock position in the right posterior and left anterior cavities (mean ± sd STL 87% ± 15% vs 46% ± 38% and 78% ± 35% vs 43% ± 24%, respectively; P < 0.05), and on the right posterior surfaces of the middle‐lower/lower cavities (PBL 72% vs 31% and 77% vs 35%, respectively; P < 0.01) and on the left lateral surface of the lower cavities (PBL 45% vs 25%; P = 0048), respectively. Conversely, the 9 o’clock position provided higher STLs and PBLs than the 3 o’clock position in the left posterior and right anterior cavities (mean ± sd STL 84% ± 20% vs 65% ± 28% and 79% ± 30% vs 44% ± 35%, respectively; P ≤ 0.02), and on the left posterior and right lateral surfaces of the lower cavities (PBL 59% vs 34% and 50% vs 21%, respectively; P ≤ 0.04).ConclusionsThe position of the working channel of the flexible ureteroscope should be considered when planning flexible ureteroscopy, especially when dealing with the lower pole.
Stereotactic radiotherapy for prostate bed recurrence after prostatectomy, a multicentric series
Authors: Francolini Giulio , Jereczek‐Fossa Barbara Alicja , Di Cataldo Vanessa , Simontacchi Gabriele , Marvaso Giulia , Zerella Maria Alessia , Gentile Piercarlo , Bianciardi Federico , Allegretta Sara , Detti Beatrice , Masi Laura , lo Russo Monica , Livi Lorenzo 
Published: October 2019

ObjectiveTo assess the safety and effectiveness of stereotactic salvage radiotherapy (SSRT) in RT‐naïve patients affected by macroscopic prostate bed recurrence.Patients and methodsConsecutive patients treated for prostate bed macroscopic recurrence in three different Italian institutes were reviewed. Patients were treated with SSRT, with a total dose of 30–40 Gy in five fractions, the mean pre‐SSRT PSA level was 2.3 ng/mL. Two different PSA thresholds were defined and biochemical recurrence‐free survival (BCRFS) was reported, in order to better express outcome: BCRFS1 (a PSA level increase of >10% compared to the pre‐SSRT value) and BCRFS2 (a PSA level increase of >0.2 ng/mL for patients with a PSA nadir of <0.2 ng/mL or two consecutive PSA level increases of >25% compared to nadir in patients with a PSA nadir of <0.2 ng/mL).ResultsIn all, 90 patients were treated, with a mean (range) follow‐up of 21.2 (2–64) months, and 17 of these patients (19%) had concomitant androgen‐deprivation therapy (ADT) during SSRT. Complete biochemical response, defined as a PSA nadir of <0.2 ng/mL, was obtained in 39 of the 90 patients (43.3%). Considering BCRFS1, 25 patients (27.8%) had BCR, with an actuarial median BCRFS1 time of 36.4 months. For BCRFS2, BCR was reported in 32 patients (35.5%), with an actuarial median BCRFS2 time of 24.3 months. There was no Grade >2 toxicity.ConclusionsSSRT was found to yield significant biochemical control and allowed ADT delay despite adverse features.
Monetary base and federal government debt in the long‐run: A non‐linear analysis
Authors: Ahmed Haydory Akbar 
Published: October 2019

AbstractGovernment bonds are usually traded between the financial institutions and the Fed during the open market operations. These operations impact the bank reserves, subsequently influencing the monetary base. The monetary base and government bonds may portray a common trend and government debt could potentially bind the central bank to debt monetization. This paper, using monthly data on federal government debt and the monetary base from 1947:1 to 2018:10, investigates the presence of a long‐run equilibrium relationship between the two variables and as to how the long‐run equilibrium relationship vary in the short‐run. Threshold cointegration tests find evidence of a long‐run equilibrium relationship. Estimates of the threshold vector error‐correction model find statistically significant evidence of contraction in the monetary base growth in the short‐run in regime 1. In regime 2, the growth in the monetary base does not adjust to accommodate faster government debt growth. These estimates find no evidence of debt monetization or otherwise in either of the regimes in the United States. The Fed, by reducing the monetary base, perhaps focuses more on the inflation target. The findings also suggest a potential scenario where the Fed and the fiscal authority are not conjoined with each other in their operations.
Individual differences in the acquisition of non‐linguistic audio‐visual associations in 5 year olds
Authors: Altarelli Irene , Dehaene‐Lambertz Ghislaine , Bavelier Daphne 
Published: October 2019

AbstractAudio‐visual associative learning – at least when linguistic stimuli are employed – is known to rely on core linguistic skills such as phonological awareness. Here we ask whether this would also be the case in a task that does not manipulate linguistic information. Another question of interest is whether executive skills, often found to support learning, may play a larger role in a non‐linguistic audio‐visual associative task compared to a linguistic one. We present a new task that measures learning when having to associate non‐linguistic auditory signals with novel visual shapes. Importantly, our novel task shares with linguistic processes such as reading acquisition the need to associate sounds with arbitrary shapes. Yet, rather than phonemes or syllables, it uses novel environmental sounds – therefore limiting direct reliance on linguistic abilities. Five‐year‐old French‐speaking children (N = 76, 39 girls) were assessed individually in our novel audio‐visual associative task, as well as in a number of other cognitive tasks evaluating linguistic abilities and executive functions. We found phonological awareness and language comprehension to be related to scores in the audio‐visual associative task, while no correlation with executive functions was observed. These results underscore a key relation between foundational language competencies and audio‐visual associative learning, even in the absence of linguistic input in the associative task.
Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells
Authors: Jing Ruihua , Qi Tiantian , Wen Chan , Yue Jiaqi , Wang Guangyan , Pei Cheng , Ma Bo 
Published: October 2019

AbstractMacular fibrosis is a vital obstacle of vision acuity improvement of age‐related macular degeneration patients. This study was to investigate the effects of interleukin 2 (IL‐2) on epithelial‐mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and transforming growth factor β2 (TGF‐β2) expression in retinal pigment epithelial (RPE) cells. 10 μg/L IL‐2 was used to induce fibrosis in RPE cells for various times. Western blot was used to detect the EMT marker α‐smooth muscle actin (α‐SMA), ECM markers fibronectin (Fn) and type 1 collagen (COL‐1), TGF‐β2, and the activation of the JAK/STAT3 and NF‐κB signaling pathway. Furthermore, JAK/STAT3 and NF‐κB signaling pathways were specifically blocked by WP1066 or BAY11‐7082, respectively, and the expression of α‐SMA, COL‐1, Fn and TGF‐β2 protein were detected. Wound healing and Transwell assays were used to measure cell migration ability of IL‐2 with or without WP1066 or BAY11‐7082. After induction of IL‐2, the expressions of Fn, COL‐1, TGF‐β2 protein were significantly increased, and this effect was correlated with IL‐2 treatment duration, while α‐SMA protein expression did not change significantly. Both WP1066 and BAY11‐7082 could effectively downregulate the expression of Fn, COL‐1 and TGF‐β2 induced by IL‐2. What's more, both NF‐κB and JAK/STAT3 inhibitors could suppress the activation of the other signaling pathway. Additionally, JAK/STAT3 inhibitor WP1066 and NF‐κB inhibitor BAY 11‐7082 could obviously decrease RPE cells migration capability induced by IL‐2. IL‐2 promotes cell migration, ECM synthesis and TGF‐β2 expression in RPE cells via JAK/STAT3 and NF‐κB signaling pathways, which may play an important role in proliferative vitreoretinopathy.
WORK HISTORIES AND LIFETIME UNEMPLOYMENT
Authors: Morchio Iacopo 
Published: October 2019

AbstractA long‐standing question in economics is how important unobserved differences across workers are for explaining unemployment. I revisit this topic using variation in lifetime unemployment across workers in U.S. data. A comparison of workers often unemployed with the rest shows that although differences in job‐finding rates increase over the course of a career, differences in job‐separation rates are large right from the start. I develop a directed search model with symmetric unobserved heterogeneity, in which agents learn workers' types from their labor market histories, to rationalize these findings. The model cannot match the data if unobserved heterogeneity is neglected.
The Impermanence of Permanence: The Rise of Probationary Immigration in Canada
Authors: Ellermann Antje , Gorokhovskaia Yana 
Published: October 2019

AbstractThis article engages with arguments that contemporary immigration politics is defined by a “loss of settlement” by examining recent developments in Canadian immigration and refugee policy that have made permanent residence less permanent. We suggest that the rise of probationary immigration has been facilitated by horizontal status stratification within groups that were historically marked by relative status equality. In order to examine this claim empirically in the Canadian context, we analyze the rise of temporary foreign worker recruitment, the move from “one‐step” to “two‐step” immigration, and changes to refugee policy that, for the first time, linked loss of refugee status to the loss of permanent resident status.
Deciphering host immunity to malaria using systems immunology
Authors: Loiseau Claire , Cooper Martha M. , Doolan Denise L. 
Published: October 2019

AbstractA century of conceptual and technological advances in infectious disease research has changed the face of medicine. However, there remains a lack of effective interventions and a poor understanding of host immunity to the most significant and complex pathogens, including malaria. The development of successful interventions against such intractable diseases requires a comprehensive understanding of host‐pathogen immune responses. A major advance of the past decade has been a paradigm switch in thinking from the contemporary reductionist (gene‐by‐gene or protein‐by‐protein) view to a more holistic (whole organism) view. Also, a recognition that host‐pathogen immunity is composed of complex, dynamic interactions of cellular and molecular components and networks that cannot be represented by any individual component in isolation. Systems immunology integrates the field of immunology with omics technologies and computational sciences to comprehensively interrogate the immune response at a systems level. Herein, we describe the system immunology toolkit and report recent studies deploying systems‐level approaches in the context of natural exposure to malaria or controlled human malaria infection. We contribute our perspective on the potential of systems immunity for the rational design and development of effective interventions to improve global public health.
Genetic structure of endangered lake chubsucker Erimyzon sucetta in Canada reveals a differentiated population in a precarious habitat
Authors: Hauser Frances E. , Fontenelle João P. , Elbassiouny Ahmed A. , Mandrak Nicholas E. , Lovejoy Nathan R. 
Published: October 2019

AbstractWe used mitochondrial DNA to assess the genetic structure of endangered lake chubsucker Erimyzon sucetta across its Canadian range. We found unique mitochondrial haplotypes in Lyons Creek, a tributary of the Niagara River that faces a strong potential for habitat deterioration. Lyons Creek may therefore serve as a reservoir of unique genetic diversity. The sensitivity of Lyons Creek, combined with the genetic uniqueness of its E. sucetta population, call for further investigation into whether this population should be considered a separate designatable unit for conservation purposes.
Niemann–Pick type C disease: cellular pathology and pharmacotherapy
Authors: Wheeler Simon , Sillence Dan J. 
Published: October 2019

AbstractNiemann–Pick type C disease (NPCD) was first described in 1914 and affects approximately 1 in 150 000 live births. It is characterized clinically by diverse symptoms affecting liver, spleen, motor control, and brain; premature death invariably results. Its molecular origins were traced, as late as 1997, to a protein of late endosomes and lysosomes which was named NPC1. Mutation or absence of this protein leads to accumulation of cholesterol in these organelles. In this review, we focus on the intracellular events that drive the pathology of this disease. We first introduce endocytosis, a much‐studied area of dysfunction in NPCD cells, and survey the various ways in which this process malfunctions. We briefly consider autophagy before attempting to map the more complex pathways by which lysosomal cholesterol storage leads to protein misregulation, mitochondrial dysfunction, and cell death. We then briefly introduce the metabolic pathways of sphingolipids (as these emerge as key species for treatment) and critically examine the various treatment approaches that have been attempted to date.
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Distinct gradients of various neurotransmitter markers in caudate nucleus and putamen of the human brain
Authors: Hörtnagl Heide , Pifl Christian , Hörtnagl Erik , Reiner Angelika , Sperk Günther 
Published: October 2019

AbstractThe caudate nucleus (CN) and the putamen (PUT) as parts of the human striatum are distinguished by a marked heterogeneity in functional, anatomical, and neurochemical patterns. Our study aimed to document in detail the regional diversity in the distribution of dopamine (DA), serotonin, γ‐aminobuturic acid, and choline acetyltransferase within the CN and PUT. For this purpose we dissected the CN as well as the PUT of 12 post‐mortem brains of human subjects with no evidence of neurological and psychiatric disorders (38–81 years old) into about 80 tissue parts. We then investigated rostro‐caudal, dorso‐ventral, and medio‐lateral gradients of these neurotransmitter markers. All parameters revealed higher levels, turnover rates, or activities in the PUT than in the CN. Within the PUT, DA levels increased continuously from rostral to caudal. In contrast, the lowest molar ratio of homovanillic acid to DA, a marker of DA turnover, coincided with highest DA levels in the caudal PUT, the part of the striatum with the highest loss of DA in Parkinson’s disease (N. Engl. J. Med., 318, 1988, 876). Highest DA concentrations were found in the most central areas both in the PUT and CN. We observed an age‐dependent loss of DA in the PUT and CN that did not correspond to the loss described for Parkinson’s disease indicating different mechanisms inducing the deficit of DA. Our data demonstrate a marked heterogeneity in the anatomical distribution of neurotransmitter markers in the human dorsal striatum indicating anatomical and functional diversity within this brain structure.
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Efficacy of anti‐inflammatory moisturizer vs hydrophilic cream in elderly patients with moderate to severe xerosis: A split site, triple‐blinded, randomized, controlled trial
Authors: Lueangarun Suparuj , Soktepy Bith , Tempark Therdpong 
Published: October 2019

AbstractBackgroundXerosis is a common problem among the elderly, characterized by dry‐scaling erythema, fissuring, or pruritus, which could be treated by anti‐inflammatory moisturizers without side effects of steroids.AimsWe aimed to investigate the efficacy of anti‐inflammatory moisturizer (MAS062D lotion) vs hydrophilic cream for the improvement of dry and barrier function skin in xerosis patients.MethodsA split site, triple‐blinded, randomized, controlled trial was conducted in the elderly with moderate to severe xerosis, who received the 28‐day twice daily application of MAS062D lotion and hydrophilic cream on the assigned shins. The evaluations on day 0, 14, and 28 were performed using clinical assessment, skin hydration by corneometer, transepidermal water loss (TEWL), and biometric assessment.ResultsThere were 24 Thai elderly patients, of whom 87.5% were female (mean age = 58.04 years and mean xerosis severity scale (XSS) = 4.83). Both treatments revealed similar statistically significant improvement in XSS (P < .001). Interestingly, MAS062D lotion–treated side remarkably showed improvement of skin hydration compared with hydrophilic‐treated side for 26.86 ± 7.94 vs 25.84 ± 5.1, 41.24 ± 6.92 vs 20.96 ± 6.8, 50.49 ± 8.2 vs 21.75 ± 8.29 at baseline, day 14, and 28, respectively (P‐value < .001). Moreover, MAS062D lotion significantly yielded greater decrease in TEWL measurement and more erythema improvement than hydrophilic cream (P‐value < .001). No serious adverse effects were observed with either treatment.ConclusionThe MAS062D lotion could potentially be an efficacious treatment for improvement of xerosis in the elderly, which is also safe and refrains from steroid side effects.
The Lhx4 homeobox transcript in the rat pineal gland: Adrenergic regulation and impact on transcripts encoding melatonin‐synthesizing enzymes
Authors: Hertz Henrik , Carstensen Mikkel B. , Bering Tenna , Rohde Kristian , Møller Morten , Granau Agnete M. , Coon Steven L. , Klein David C. , Rath Martin F. 
Published: October 2019

AbstractHomeobox genes generally encode transcription factors involved in regulating developmental processes. In the pineal gland, a brain structure devoted to nocturnal melatonin synthesis, a number of homeobox genes are also expressed postnatally; among these is the LIM homeobox 4 gene (Lhx4). We here report that Lhx4 is specifically expressed in the postnatal pineal gland of rats and humans. Circadian analyses revealed a fourfold rhythm in Lhx4 expression in the rat pineal gland, with rhythmic expression detectable from postnatal day 10. Pineal Lhx4 expression was confirmed to be positively driven by adrenergic signaling, as evidenced by in vivo modulation of Lhx4 expression by pharmacological (isoprenaline injection) and surgical (superior cervical ganglionectomy) interventions. In cultured pinealocytes, Lhx4 expression was upregulated by cyclic AMP, a second messenger of norepinephrine. By use of RNAscope technology, Lhx4 transcripts were found to be exclusively localized in melatonin‐synthesizing pinealocytes. This prompted us to investigate the possible role of Lhx4 in regulation of melatonin‐producing enzymes. By use of siRNA technology, we knocked down Lhx4 by 95% in cultured pinealocytes; this caused a reduction in transcripts encoding the melatonin‐producing enzyme arylalkylamine N‐acetyl transferase (Aanat). Screening the transcriptome of siRNA‐treated pinealocytes by RNAseq revealed a significant impact of Lhx4 on the phototransduction pathway and on transcripts involved in development of the nervous system and photoreceptors. These data suggest that rhythmic expression of Lhx4 in the pineal gland is controlled via an adrenergic‐cyclic AMP mechanism and that Lhx4 acts to promote nocturnal melatonin synthesis.