bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase transitions in few-monolayer spin ice films
Authors: Bovo L. , Rouleau C. M. , Prabhakaran D. , Bramwell S. T. 
Published: March 2019

AbstractVertex models are an important class of statistical mechanical system that admit exact solutions and exotic physics. Applications include water ice, ferro- and antiferro-electrics, spin ice and artificial spin ice. Here we show that it is possible to engineer spin ice films with atomic-layer precision down to the monolayer limit. Specific heat measurements show that these films, which have a fundamentally different symmetry to bulk spin ice, realise systems close to the two-dimensional F-model, with exotic phase transitions on topologically-constrained configurational manifolds. Our results show how spin ice thin films can release the celebrated Pauling entropy of spin ice without an anomaly in the specific heat. They also significantly expand the class of vertex models available to experiment.
TNFα is responsible for the canonical offspring number-size trade-off
Authors: Maslennikova S. O. , Gerlinskaya L. A. , Kontsevaya G. V. , Anisimova M. V. , Nedospasov S. A. , Feofanova N. A. , Moshkin M. P. , Moshkin Y. M. 
Published: March 2019

AbstractThere is a canonical life-history trade-off between quantity and quality of offspring, but molecular determinants for this are unknown. Here, we show that knockout of tumor necrosis factor (TNF-KO) in mice switched a relation between the number and size of developing embryos from expectedly negative to unexpectedly positive. Depletion of TNFα imbalanced humoral and trophic maintenance of embryo growth during gestation with respect to the litter size. The levels of embryotrophic GM-CSF cytokine and placental efficiency attained positive correlations with the number and size of embryos in TNF-KO females. Thus, TNFα oversees mother’s resource allocations to balance embryo growth with the number of offspring. Consequently, this suggests an intricate link between the number-size trade-off and immunity given a pivotal role of TNFα in immune homeostasis.
Automated real-time quantification of group locomotor activity in Drosophila melanogaster
Authors: Scaplen Kristin M. , Mei Nicholas J. , Bounds Hayley A. , Song Sophia L. , Azanchi Reza , Kaun Karla R. 
Published: March 2019

AbstractRecent advances in neurogenetics have highlighted Drosophila melanogaster as an exciting model to study neural circuit dynamics and complex behavior. Automated tracking methods have facilitated the study of complex behaviors via high throughput behavioral screening. Here we describe a newly developed low-cost assay capable of real-time monitoring and quantifying Drosophila group activity. This platform offers reliable real-time quantification with open source software and a user-friendly interface for data acquisition and analysis. We demonstrate the utility of this platform by characterizing ethanol-induced locomotor activity in a dose-dependent manner as well as the effects of thermo and optogenetic manipulation of ellipsoid body neurons important for ethanol-induced locomotor activity. As expected, low doses of ethanol induced an initial startle and slow ramping of group activity, whereas high doses of ethanol induced sustained group activity followed by sedation. Advanced offline processing revealed discrete behavioral features characteristic of intoxication. Thermogenetic inactivation of ellipsoid body ring neurons reduced group activity whereas optogenetic activation increased activity. Together, these data establish the fly Group Activity Monitor (flyGrAM) platform as a robust means of obtaining an online read out of group activity in response to manipulations to the environment or neural activity, with an opportunity for more advanced post-processing offline.
Molybdenum-isotope signals and cerium anomalies in Palaeoproterozoic manganese ore survive high-grade metamorphism
Authors: Cabral Alexandre Raphael , Zeh Armin , Vianna Nívea Cristina , Ackerman Lukáš , Pašava Jan , Lehmann Bernd , Chrastný Vladislav 
Published: March 2019

AbstractMolybdenum (Mo) and its isotopes have been used to retrieve palaeoenvironmental information on the ocean–atmosphere system through geological time. Their application has so far been restricted to rocks least affected by severe metamorphism and deformation, which may erase or alter palaeoenvironmental signals. Environmental Mo-isotope signatures can be retrieved if the more manganese (Mn)-enriched rocks are isotopically depleted and the maximum range of δ98Mo values is close to the ~2.7‰ Mo-isotope fractionation known from Mo sorption onto Mn oxides at low temperature. Here, we show that the Morro da Mina Mn-ore deposit in Minas Gerais, Brazil, contains Mn-silicate–carbonate ore and associated graphitic schist that likely preserve δ98Mo of Palaeoproterozoic seawater, despite a metamorphic overprint of at least 600 °C. The extent of Mo-isotope fractionation between the Mn-silicate–carbonate ore and the graphitic schist is similar to modern Mn-oxide precipitates and seawater. Differences in δ98Mo signals are broadly reflected in cerium (Ce) anomalies, which suggest an oxic–anoxic-stratified Palaeoproterozoic ocean.
Renal expression of JAK2 is high in polycystic kidney disease and its inhibition reduces cystogenesis
Authors: Patera Foteini , Cudzich-Madry Alex , Huang Zhi , Fragiadaki Maria 
Published: March 2019

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is the most common renal genetic disorder, however it still lacks a cure. The discovery of new therapies heavily depends on understanding key signalling pathways that lead to ADPKD. The JAnus Kinase and Signal Transducers and Activators of Transcription (JAK/STAT) pathway is aberrantly activated and contributes to ADPKD pathogenesis via enhancing epithelial proliferation. Yet the mechanisms underlying the upregulation of JAK/STAT activity in this disease context is completely unknown. Here, we investigate the role of JAK2 in ADPKD using a murine model of ADPKD (Pkd1nl/nl). In normal kidneys, JAK2 expression is limited to tubular epithelial and vascular cells with lesser staining in bowman’s capsule and remains below detection level in the interstitium. By contrast, in kidneys of mice with ADPKD, JAK2 is higher in cyst-lining cells when compared to normal tubules and critically, it is ectopically expressed in the interstitium, suggesting that ectopic JAK2 may contribute to ADPKD. JAK2 activity was inhibited using either curcumin, a natural compound with strong JAK2 inhibitor activity, or Tofacitinib, a clinically used selective JAK small molecule inhibitor. JAK2 inhibition led to significantly reduced tyrosine phosphorylation of STAT3 and markedly reduced cystic growth of human and mouse ADPKD-derived cells in cystogenesis assays. Taken together, our results indicate that blockade of JAK2 shows promise as a novel therapeutic target in ADPKD.
Non-redundant functions of FAK and Pyk2 in intestinal epithelial repair
Authors: Thomas Keena S. , Owen Katherine A. , Conger Kathryn , Llewellyn Ryan A. , Bouton Amy H. , Casanova James E. 
Published: March 2019

AbstractAdhesion signaling between epithelial cells and the extracellular matrix plays a critical role in maintaining tissue homeostasis and the response to tissue damage. Focal adhesion kinase (FAK) and its close relative Pyk2 are non-receptor tyrosine kinases that mediate adhesion signaling to promote cell proliferation, motility and survival. FAK has also been shown to act as a mechanosensor by modulating cell proliferation in response to changes in tissue compliance. We previously showed that mice lacking FAK in the intestinal epithelium are phenotypically normal under homeostatic conditions but hypersensitive to experimental colitis induced by dextran sulfate sodium (DSS). Here we report that Pyk2-deficient mice are also phenotypically normal under homeostatic conditions and are similarly hypersensitive to DSS-induced colitis. These data indicate that normal intestinal development and homeostatic maintenance can occur in the presence of either FAK or Pyk2, but that both kinases are necessary for epithelial repair following injury. In contrast, mice lacking both FAK and Pyk2 develop spontaneous colitis with 100% penetrance by 4 weeks of age. Normal colonic phenotype and function are restored upon treatment of the double knockout mice with antibiotics, implicating commensal bacteria or bacterial products in the etiology of the spontaneous colitis exhibited by these mice.
MicroRNA-26a reduces synovial inflammation and cartilage injury in osteoarthritis of knee joints through impairing the NF-κB signaling pathway
Authors: Zhao Zhi , Dai Xiu-Song , Wang Zhi-Yan , Bao Zheng-Qi , Guan Jian-Zhong 
Published: March 2019

Abstract
Objective: Inflammation is closely implicated in the process of osteoarthritis (OA) and affects disease progression and pain. Herein, the present study explored the effect of microRNA-26a (miR-26a) on the synovial inflammation and cartilage injury in OA, with the involvement with the NF-κB signaling pathway.
Methods: Rat models of OA were established by anterior cruciate ligament transection, which were then treated with miR-26a mimics/inhibitors or BMS-345541 (inhibitor of NF-κB pathway). The expression of miR-26a and activator proteins of NF-κB pathway (P-IκBα and P-P65) in synovial tissues was determined. Hematoxylin-eosin (HE) staining was adopted to observe pathological changes of knee joints, synovial tissues, and cartilage of femoral condyle. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the apoptosis of synoviocytes and chondrocytes.
Results: Poorly expressed miR-26a and increased protein levels of P-IκBα and P-P65 were identified in synovial tissues of OA rats. Besides, OA rats showed obvious synovial tissue hyperplasia, inflammation and cartilage injury of femoral condyle, as well as increased inflammation and cartilage injury scores, and apoptosis of synoviocytes and chondrocytes. In response to miR-26a mimics, protein levels of P-IκBα and P-P65 were reduced; meanwhile, synovial tissue hyperplasia, inflammation and cartilage injury of femoral condyle were ameliorated, with decreased inflammation and cartilage injury scores, and apoptosis of synoviocytes and chondrocytes.
Conclusion: MiR-26a suppressed the activation of the NF-κB signaling pathway, by which mechanism the synovial inflammation and cartilage injury in OA rats were alleviated.
Osteogenic protein-1 alleviates high glucose microenvironment-caused degenerative changes in nucleus pulposus cells
Authors: Liu Ziming , Zhang Zhiwen , Zhang Ali , Zhang Fan , Du Wennan , Zhang Yongqiang , Zhang Rongfeng , Xu Jiagang , Wu Xiangkun , Zhang Chengmin , Li Ning , Tan Qi , Huang Wei 
Published: March 2019

Abstract
Increasing evidence has indicated a close relationship between diabetes mellitus (DM) and disc degeneration. As a potential therapeutic growth factor, osteogenic protein-1 (OP-1) has lots of protective effects on the healthy disc cell’s biology. The present study was aimed to investigate the effects of OP-1 on degenerative changes of nucleus pulposus (NP) cells in a high glucose culture. Rat NP cells were cultured in the baseline medium or the high glucose (0.2 M) culture medium. OP-1 was added into the high glucose culture medium to investigate whether its has some protective effects against degenerative changes of NP cells in the high glucose culture. NP cell apoptosis ratio, caspase-3/9 activity, expression of apoptosis-related molecules (Bcl-2, Bax, and caspase-3), matrix macromolecules (aggrecan and collagen II), and matrix remodeling enzymes (MMP-3, MMP-13, and ADAMTS-4), and immuno-staining of NP matrix proteins (aggrecan and collagen II) were evaluated. Compared with the baseline culture, high glucose culture significantly increased NP cell apoptosis ratio, caspase-3/9 activity, up-regulated expression of Bax, caspase-3, MMP-3, MMP-13 and ADAMTS-4, down-regulated expression of Bcl-2, aggrecan and collagen II, and decreased staining intensity of aggrecan and collagen II. However, the results of these parameters were partly reversed by the addition of OP-1 in the high glucose culture. OP-1 can alleviate high glucose microenvironment-induced degenerative changes of NP cells. The present study provides that OP-1 may be promising in retarding disc degeneration in DM patients.
Development of therapeutic genome engineering in laminin-α2-deficient congenital muscular dystrophy
Authors: Kemaladewi Dwi U. , Cohn Ronald D. 
Published: March 2019

Abstract
Muscular dystrophies are a heterogeneous group of genetic muscle diseases that are often characterized by pathological findings of muscle fiber degeneration and the replacement of muscle fibers with fibrotic/connective tissues. In spite of the genetic causes of many of these conditions having been identified, curative treatments are still lacking. Recently, genome engineering technologies, including targeted gene editing and gene regulation, have emerged as attractive therapeutic tools for a variety of muscular dystrophies. This review summarizes the genome engineering strategies that are currently under preclinical evaluation for the treatment of LAMA2-deficient congenital muscular dystrophy. In particular, we focus on the applications of CRISPR/Cas9 to correct a splice site mutation in LAMA2 and to up-regulate a disease-modifying gene LAMA1. Finally, the challenges faced in the clinical translation of these strategies are discussed.
The Therapeutic Hypothermia in Treatment of Hyperammonemic Encephalopathy due to Urea Cycle Disorders and Organic Acidemias
Authors: Ninković Dorotea , Mustapić Željka , Bartoniček Dorotea , Benjak Vesna , Ćuk Mario , Buljević Andrea , Grčić Boris , Fumić Ksenija , Grizelj Ruža , Lehman Ivan , Ramadža Danijela , Sarnavka Vladimir , Slaviček Jasna , Kastelić Jasminka , Barišić Nina , Barić Ivo 
Published: March 2019

Abstract
Background Hyperammonemic encephalopathy in newborns with urea cycle disorders and certain organic acidurias can cause severe brain injury, coma and death. Standard therapy includes protein restriction, nitrogen-scavenging drugs, prevention of catabolism and hemodialysis. Neuroprotective hypothermia as part of the treatment has been reported only 3 times. It has been suggested that mild systemic hypothermia can contribute to better neurological outcomes in hyperammonemic encephalopathy. However, the limited experience precludes accurate conclusions on safety and efficacy.
Methods Whole body therapeutic hypothermia was included in the standard treatment of hyperammonemic encephalopathy in 4 neonates with urea cycle disorder or organic aciduria.
Results Two patients survived the initial crisis. One patient has a developmental quotient of 0.8, while the other shows severe developmental delay. The cooling protocol had to be discontinued in 3 patients due to the otherwise untreatable complications (hypotension and hemorrhage).
Conclusion The efficacy and safety of therapeutic hypothermia in the treatment of neonatal hyperammonemic encephalopathy depend on various factors, requiring further evaluation.
CyTOFmerge: integrating mass cytometry data across multiple panels
Authors: Abdelaal Tamim , Höllt Thomas , van Unen Vincent , Lelieveldt Boudewijn P F , Koning Frits , Reinders Marcel J T , Mahfouz Ahmed 
Published: March 2019

Abstract

Motivation
High-dimensional mass cytometry (CyTOF) allows the simultaneous measurement of multiple cellular markers at single-cell level, providing a comprehensive view of cell compositions. However, the power of CyTOF to explore the full heterogeneity of a biological sample at the single-cell level is currently limited by the number of markers measured simultaneously on a single panel.

Results
To extend the number of markers per cell, we propose an in silico method to integrate CyTOF datasets measured using multiple panels that share a set of markers. Additionally, we present an approach to select the most informative markers from an existing CyTOF dataset to be used as a shared marker set between panels. We demonstrate the feasibility of our methods by evaluating the quality of clustering and neighborhood preservation of the integrated dataset, on two public CyTOF datasets. We illustrate that by computationally extending the number of markers we can further untangle the heterogeneity of mass cytometry data, including rare cell-population detection.

Availability and implementation
Implementation is available on GitHub (https://github.com/tabdelaal/CyTOFmerge).

Supplementary information
Supplementary data are available at Bioinformatics online.
Computerized Cognitive Training for Older Adults at Higher Dementia Risk due to Diabetes: Findings From a Randomized Controlled Trial
Authors: Bahar-Fuchs Alex , Barendse Marjolein E A , Bloom Rachel , Ravona-Springer Ramit , Heymann Anthony , Dabush Hai , Bar Lior , Slater-Barkan Shirel , Rassovsky Yuri , Schnaider Beeri Michal 
Published: March 2019

Abstract

Background
To evaluate the effects of adaptive and tailored computerized cognitive training on cognition and disease self-management in older adults with diabetes.

Methods
This was a single-blind trial. Eighty-four community-dwelling older adults with diabetes were randomized into a tailored and adaptive computerized cognitive training or a generic, non-tailored or adaptive computerized cognitive training condition. Both groups trained for 8 weeks on the commercially available CogniFit program and were supported by a range of behavior change techniques. Participants in each condition were further randomized into a global or cognition-specific self-efficacy intervention, or to a no self-efficacy condition. The primary outcome was global cognition immediately following the intervention. Secondary outcomes included diabetes self-management, meta-memory, mood, and self-efficacy. Assessments were conducted at baseline, immediately after the training, and at a 6-month follow-up.

Results
Adherence and retention were lower in the generic computerized cognitive training condition, but the self-efficacy intervention was not associated with adherence. Moderate improvements in performance on a global cognitive composite at the posttreatment assessments were observed in both cognitive training conditions, with further small improvement observed at the 6-month follow-up. Results for diabetes self-management showed a modest improvement on self-rated diabetes care for both intervention conditions following the treatment, which was maintained at the 6-month follow-up.

Conclusions
Our findings suggest that older adults at higher dementia risk due to diabetes can show improvements in both cognition and disease self-management following home-based multidomain computerized cognitive training. These findings also suggest that adaptive difficulty and individual task tailoring may not be critical components of such interventions.

Trial registration
NCT02709629.
Lack of NLRP3 Inflammasome Activation Reduces Age-Dependent Sarcopenia and Mitochondrial Dysfunction, Favoring the Prophylactic Effect of Melatonin
Authors: Sayed Ramy K A , Fernández-Ortiz Marisol , Diaz-Casado María E , Aranda-Martínez Paula , Fernández-Martínez José , Guerra-Librero Ana , Escames Germaine , López Luis C , Alsaadawy Reem M , Acuña-Castroviejo Darío 
Published: March 2019

Abstract
To investigate the role of NLRP3 inflammasome in muscular aging, we evaluated here the morphological and functional markers of sarcopenia in the NLRP3-knockout mice, as well as the beneficial effect of melatonin supplementation. The gastrocnemius muscles of young (3 months), early-aged (12 months), and old-aged (24 months) NLRP3-knockout female mice were examined. Moreover, locomotor activity and apoptosis were assessed. The results revealed early markers of sarcopenia at the age of 12 months, including reduction of lactate, ratio of muscle weight to body weight, muscle fibers number, and mitochondrial number. Increased interstitial tissues, apoptosis, and muscle fibers area, as well as mitochondrial damage were detected, with little muscular activity effects. In the old-aged, these alterations progressed with a reduction in locomotor activity, mitochondrial cristae destruction, nuclear fragmentation, tubular aggregates (TAs) formation, and increased frailty index. Oral melatonin supplementation preserved the normal muscular structure, muscle fibers number, and muscular activity in old age. Melatonin enhanced lactate production, recovered mitochondria, inhibited TAs formation, reduced apoptosis, and normalized frailty index. The fewer sarcopenic changes as well as the highly detectable prophylactic effects of melatonin treatment reported here in the muscle of NLRP3-knockout mice comparing with that previously detected in wild-type mice, confirming NLRP3 inflammasome implication in muscular aging and sarcopenia onset and progression.
Central Banking’s Long March over the Decades
Authors: Mayes David G. , Siklos Pierre L. , Sturm Jan-Egbert 
Published: March 2019

Abstract
This chapter covers central bank topics including governance, independence, balance-sheet and crisis management, and challenges in macroeconomic modeling. It is intended as a summary of current and potential challenges faced by central banks in monetary policy and maintenance of financial system stability. The chapter covers a variety of views about past and present behavior and performance of central banks around the world, providing a state-of-the-art perspective on likely future challenges to be faced by this critical institution. The chapter points out gaps where future research is likely to be fruitful and the questions and issues that remain unanswered. One motivation for the book is the financial crisis of 2007–2009. Nevertheless, several themes covered and analyzed predate the crisis. The aftermath of the crisis also raised new questions about the scope, influence, and response of central banks in a changing macroeconomic landscape. The chapter also touches on fintech and digital currencies.
Transparency of Monetary Policy in the Postcrisis World
Authors: Dincer Nergiz , Eichengreen Barry , Geraats Petra 
Published: March 2019

Abstract
This chapter analyzes whether and to what extent central banks have continued to be more transparent in their conduct of monetary policy in the postcrisis period. It presents a monetary policy transparency index, that measures the degree of information disclosure about various aspects of the policymaking process for 112 central banks from 1998 until 2015. Compared to previous research, the index has been updated, revised and refined to better capture developments since the global financial crisis, with and explicit focus on monetary policy, more emphasis on the timely disclosure of information, and greater granularity, including for forward guidance. The development and challenges of increasing monetary policy transparency are further analyzed in case studies of the European Central Bank, the US Federal Reserve and the Bank of England, which illustrate how these prominent central banks have deployed greater transparency as a policy tool in the aftermath of the financial crisis.
Real Estate, Construction, Money, Credit, and Finance
Authors: Sinclair Peter 
Published: March 2019

Abstract
This chapter examines the interactions between real estate markets on the one side and, on the other, interest rates, credit, and financial variables. A simple model is set up to analyze the key ideas, which will yield long run equilibrium values for the housing stock and the price of dwellings. It also shows the path that these variables will take toward the long run equilibrium, provided there are no further shocks, from any initial position of the housing stock. Next, the model is extended to explore complications. The chapter then turns to the recent historical record of the links between real estate and financial crises and to relevant policy issues.