bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS
Authors: Veenstra Mike , Williams Dionna W , Calderon Tina M , Anastos Kathryn , Morgello Susan , Berman Joan W 
Published: July 2017

Abstract
CD14+CD16+ monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting &gt;50% of infected individuals. There are no therapies to reduce these deficits or to prevent CNS entry of CD14+CD16+ monocytes. The goal of this study was to determine whether CXCR7, a receptor for CXCL12, is expressed on CD14+CD16+ monocytes and whether a small molecule CXCR7 antagonist (CCX771) can prevent CD14+CD16+ monocyte transmigration into the CNS. We showed for the first time that CXCR7 is on CD14+CD16+ monocytes and that it may be a therapeutic target to reduce their entry into the brain. We demonstrated that CD14+CD16+ monocytes and not the more abundant CD14+CD16− monocytes or T cells transmigrate to low homeostatic levels of CXCL12. This may be a result of increased CXCR7 on CD14+CD16+ monocytes. We showed that CCX771 reduced transmigration of CD14+CD16+ monocytes but not of CD14+CD16− monocytes from uninfected and HIV-infected individuals and that it reduced CXCL12-mediated chemotaxis of CD14+CD16+ monocytes. We propose that CXCR7 is a therapeutic target on CD14+CD16+ monocytes to limit their CNS entry, thereby reducing neuroinflammation, neuronal damage, and HIV-associated neurocognitive disorders. Our data also suggest that CCX771 may reduce CD14+CD16+ monocyte-mediated inflammation in other disorders.
L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes
Authors: Repnik Urska , Borg Distefano Marita , Speth Martin Tobias , Ng Matthew Yoke Wui , Progida Cinzia , Hoflack Bernard , Gruenberg Jean , Griffiths Gareth 
Published: July 2017

ABSTRACT
L-leucyl-L-leucine methyl ester (LLOMe) induces apoptosis, which is thought to be mediated by release of lysosomal cysteine cathepsins from permeabilized lysosomes into the cytosol. Here, we demonstrated in HeLa cells that apoptotic as well as sub-apoptotic concentrations of LLOMe caused rapid and complete lysosomal membrane permeabilization (LMP), as evidenced by loss of the proton gradient and release into the cytosol of internalized lysosomal markers below a relative molecular mass of 10,000. However, there was no evidence for the release of cysteine cathepsins B and L into the cytosol; rather they remained within lysosomes, where they were rapidly inactivated and degraded. LLOMe-induced adverse effects, including LMP, loss of cysteine cathepsin activity, caspase activation and cell death could be reduced by inhibition of cathepsin C, but not by inhibiting cathepsins B and L. When incubated with sub-apoptotic LLOMe concentrations, lysosomes transiently lost protons but annealed and re-acidified within hours. Full lysosomal function required new protein synthesis of cysteine cathepsins and other hydrolyses. Our data argue against the release of lysosomal enzymes into the cytosol and their proposed proteolytic signaling during LLOMe-induced apoptosis.
Ezrin directly interacts with AQP2 and promotes its endocytosis
Authors: Li Wei , Jin William W. , Tsuji Kenji , Chen Ying , Nomura Naohiro , Su Limin , Yui Naofumi , Arthur Julian , Cotecchia Susanna , Păunescu Teodor G. , Brown Dennis , Lu Hua A. J. 
Published: July 2017

ABSTRACT
The water channel aquaporin-2 (AQP2) is a major regulator of water homeostasis in response to vasopressin (VP). Dynamic trafficking of AQP2 relies on its close interaction with trafficking machinery proteins and the actin cytoskeleton. Here, we report the identification of ezrin, an actin-binding protein from the ezrin/radixin/moesin (ERM) family as an AQP2-interacting protein. Ezrin was first detected in a co-immunoprecipitation (co-IP) complex using an anti-AQP2 antibody in a proteomic analysis. Immunofluorescence staining revealed the co-expression of ezrin and AQP2 in collecting duct principal cells, and VP treatment caused redistribution of both proteins to the apical membrane. The ezrin–AQP2 interaction was confirmed by co-IP experiments with an anti-ezrin antibody, and by pulldown assays using purified full-length and FERM domain-containing recombinant ezrin. By using purified recombinant proteins, we showed that ezrin directly interacts with AQP2 C-terminus through its N-terminal FERM domain. Knocking down ezrin expression with shRNA resulted in increased membrane accumulation of AQP2 and reduced AQP2 endocytosis. Therefore, through direct interaction with AQP2, ezrin facilitates AQP2 endocytosis, thus linking the dynamic actin cytoskeleton network with AQP2 trafficking.
Cells lay their own tracks – optogenetic Cdc42 activation stimulates fibronectin deposition supporting directed migration
Authors: Zimmerman Seth P. , Asokan Sreeja B. , Kuhlman Brian , Bear James E. 
Published: July 2017

ABSTRACT
Rho GTPase family members are known regulators of directed migration and therefore play key roles in processes including development, the immune response and cancer metastasis. However, their individual contributions to these processes are complex. Here, we modify the activity of the two Rho GTPase family members Rac and Cdc42 by optogenetically recruiting specific guanine nucleotide exchange factor (GEF) DH or PH domains to defined regions of the cell membrane. We find that the localized activation of both GTPases produces lamellipodia in cells plated on a fibronectin substrate. By using a novel optotaxis assay, we show that biased activation can drive directional migration. Interestingly, in the absence of exogenous fibronectin, Rac activation is insufficient to produce stable lamellipodia or directional migration whereas Cdc42 activation is sufficient for these processes. We find that a remarkably small amount of fibronectin (&lt;10 puncta per protrusion) is necessary to support stable GTPase-driven lamellipodia formation. Cdc42 bypasses the need for exogenous fibronectin by stimulating cellular fibronectin deposition under the newly formed lamellipodia.
This article has an associated First Person interview with the first author of the paper.
TRIM65 triggers β-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma
Authors: Yang Yu-Feng , Zhang Mei-Fang , Tian Qiu-Hong , Zhang Chris Zhiyi 
Published: July 2017

ABSTRACT
Deregulation of ubiquitin ligases contributes to the malignant progression of human cancers. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase and has been implicated in human diseases, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we showed that TRIM65 expression was increased in HCC tissues and associated with poor outcome in two independent cohorts containing 888 patients. In vitro and in vivo data demonstrated that overexpression of TRIM65 promoted cell growth and tumor metastasis, whereas knockdown of TRIM65 resulted in opposite phenotypes. Further studies revealed that TRIM65 exerted oncogenic activities via ubiquitylation of Axin1 to activate the β-catenin signaling pathway. TRIM65 directly bound to Axin1 and accelerated its degradation through ubiquitylation. Furthermore, HMGA1 was identified as an upstream regulator of TRIM65 in HCC cells. In clinical samples, TRIM65 expression was positively correlated with the expression of HMGA1 and nuclear β-catenin. Collectively, our data indicate that TRIM65 functions as an oncogene in HCC. The newly identified HMGA1/TRIM65/β-catenin axis serves as a promising prognostic factor and therapeutic target.
Engineering mammalian cells to seek senescence-associated secretory phenotypes
Authors: Qudrat Anam , Wong Janice , Truong Kevin 
Published: July 2017

ABSTRACT
Since the removal of senescent cells in model organisms has been linked to rejuvenation and increased lifespan, senotherapies have emerged to target senescent cells for death. In particular, interleukin-6 (IL6) is a prominent senescence-associated secretory phenotype (SASP) and, thus, seeking IL6 could potentially localize engineered cells to senescent cells for therapeutic intervention. Here, we engineered a chimeric IL6 receptor (IL6Rchi) that generates a Ca2+ signal in response to IL6 stimulation. When IL6Rchi was co-expressed with an engineered Ca2+-activated RhoA (CaRQ), it enabled directed migration to IL6 in cells that have no such natural ability. Next, the removal of target cells was accomplished by the mechanism of membrane fusion and subsequent death. This work represents a first step towards engineering a cell to target senescent cells that secrete high levels of IL6. For increased specificity to senescent cells, it will likely be necessary for an engineered cell to recognize multiple SASPs simultaneously.
Never say die: death euphemisms, misunderstandings and their implications for practice
Authors: Rawlings Deborah , Tieman Jennifer J , Sanderson Christine , Parker Deborah , Miller-Lewis Lauren 
Published: July 2017

Background: A Massive Open Online Course (MOOC) on death and dying was conducted to open the dialogue around death and dying. In one activity, participants were asked to engage with language and to think of alternative words (or euphemisms) that are used to describe death. Aim: To reflect from a nursing perspective how language enables and sometimes disguises important messages and conversations. Methods: Four hundred and seventy one participants provided 3053 euphemisms. Findings: Euphemisms were varied, with many providing commentary on their purpose and use. Discussion: As a society we have become quite creative in the use of euphemisms, but need to be mindful of misunderstandings and misinterpretations which can cause embarrassment and distress in clinical situations. Conclusion: This paper describes some of the euphemisms that were provided, examining why they are used and how their use can be easily misconstrued in daily life and in clinical practice.
Experiences of patient-family caregiver dyads in palliative care during hospital-to-home transition process
Authors: Rocío López , Rojas Edier Arias , González Mabel Carrillo , Carreño Sonia , Diana Cárdenas , Gómez Olga 
Published: July 2017

Background: there are many people with advanced cancer who are cared for in the community, though little is known about patients' and family members' lived experiences during discharge from hospital to home. Objectives: to describe the experiences of the patient-family caregiver dyad during the transition from hospital to home at a National Cancer Institute in Colombia. Methods: a descriptive phenomenological approach was taken for this study. Results: Forty-one nominal codes emerged, comprising seven themes that describe the experience of the individual in palliative care and their family caregiver during the transition from hospital to home care. Conclusions: the patient-family caregiver dyad have to deal with symptoms while being confronted with the prognosis and progression of the disease at home. The economic costs in acquiring supplies needed for proper care provision are considerable. In addition there are administrative fees from consultations and accessing the health services. Emotional and spiritual support for the dyad is required.
Does orthopaedic surgery improve quality of life and function in patients with mucopolysaccharidoses?
Authors: Williams N. , Challoumas D. , Eastwood D. M. 
Published: July 2017

Purpose Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders associated with involvement of multiple organs along with a generalised skeletal dysplasia. Both haematopoetic stem cell transplant and enzyme replacement therapy have improved the outlook for patients while surgery remains high-risk and there is little information on clinical or functional outcome to justify many of the surgical procedures performed. This paper aims to summarise the orthopaedic surgical procedures in MPS patients for which quality of life (QoL) and functional data are available and to describe additional QoL and functional measurement tools of relevance to the assessment of orthopaedic outcomes in MPS. Methods We reviewed the available literature to look for reported outcomes of orthopaedic surgery to lower and upper limbs and the spine. In addition, we describe the general and MPS-specific health measures that might be of relevance to the orthopaedic surgeon. Results There is some evidence in the literature that orthopaedic surgery may improve QoL and function in some specific aspects of the MPS condition (in relation to genu valgum, carpal tunnel syndrome and trigger digits); however, the literature is sparse and consists of level 4/5 studies only. Further studies of these conditions should include QoL and functional assessment in order to confirm or refute these reports. In other areas (spine and hip), outcomes are judged largely on radiographic appearances with little clinical correlation and short follow-up; however, one long-term study of function following hip dysplasia surgery suggests poor outcomes. Anaesthetic morbidity/mortality is not insignificant in these complex patients with multi-organ involvement. Careful assessment is required, particularly when there is neurological involvement. Conclusions Orthopaedic surgeons involved with MPS patients should be encouraged to use and report measures of QoL and function with respect to musculoskeletal manifestations and response to surgery, recognising that such assessments in these complex and challenging patients may require a multidisciplinary approach.
Vertical Integration Smooths Innovation Diffusion
Authors: Filippini Luigi , Vergari Cecilia 
Published: July 2017

Abstract
Does vertical integration of an input innovator with a downstream firm entail innovation foreclosure? We study the licensing incentives of an independent input producer owning a patented product innovation which allows the downstream firms to improve the quality of their final goods. We consider two-part tariff contracts for both outside and incumbent innovators. We find that the incumbent innovator has always the incentive to license its innovation to the rival firm so that under vertical integration complete technology diffusion takes place. In contrast, the external patent holder may prefer exclusive licensing depending on the innovation size as well as on the set of allowed contracts. As a result vertical integration does not entail innovation foreclosure, rather it facilitates innovation diffusion with respect to vertical separation. As for the profitability, the vertical integration with either downstream firm is always privately profitable and it is welfare improving for large innovations: this implies that not all profitable mergers should be rejected.
Stochastic Logistic Model of the Global Financial Leverage
Authors: Smirnov Alexander D. 
Published: July 2017

AbstractDebt, as one of basic human relations, has profound effects on economic growth. Debt accumulation in the global economy was modeled by the stochastic logistic equation reflecting causality between leverage and its rate of change. The model, identifying interactions and feedbacks in aggregate behaviour of creditors and borrowers, addressed various issues of macrofinancial stability. Qualitatively diverse patterns, including the Wicksellian (normal) market, the Minsky financial bubbles and the Fisherian debt-deflation, were discerned by appropriate combinations of rates of return, spreads and leverage. The Kolmogorov-Fokker-Plank equation was used to find out the stationary gamma distribution of leverage that was instrumental for the evaluation of appropriate failure and survival functions. Two patterns corresponding to different forms of a stationary gamma distribution were recognized in the long run leverage dynamics and were simulated as scenarios of a possible system evolution. In particular, empirically parameterized asymptotical distribution indicated excessive leverage and unsustainable global debt accumulation. It underlined the necessity of comprehensive reforms aiming to decrease uncertainty, debt and leverage. Assuming these reforms were successfully implemented, global leverage distributions would have converged in the long run to a peaked gamma distribution with the mode identical to the anchor leverage. The latter corresponded to a balanced long run debt demand and supply, hence to fairly evaluated financial assets fully collateralized by real resources. A particular case of macrofinancial Tobin’s q-coefficients following the Ornstein-Ulenbeck process was studied to evaluate a reasonable range of squeezing the bloated world finance. The model was verified on data published by the IMF in Global Financial Stability Reports for the period 2003–2013.
Uncovering the Behavioral Implications of the Rational Addiction Assertion
Authors: Caputo Michael R 
Published: July 2017

AbstractThe consumption functions in Becker and Murphy's (1988) rational addiction theory are subjected to an extensive comparative dynamics analysis. They are shown to be intrinsically characterized by a symmetric and positive semidefinite matrix of generalized Slutsky-like terms. In contrast, the typical comparative dynamics expressions, comprised of the individual partial derivatives of the consumption functions with respect to the parameters and state variables, do not possess refutable implications under the basic assumptions of the theory. Only with additional sufficiently strong assumptions, of which some are identified here, can they be signed.
Gracilaria coppejansii sp. nov. (Gracilariales, Rhodophyta), a new flattened species from the Andaman coast of southern Thailand
Authors: Muangmai Narongrit , Lewmanomont Khanjanapaj , Prathep Anchana , Terada Ryuta , Zuccarello Giuseppe C. 
Published: July 2017

AbstractStudies of the taxonomy and diversity of flattened
Integrated Palm Biomass Supply Chain toward Sustainable Management
Authors: How B S , Lam H L 
Published: July 2017

Abstract
Sustainable biomass supply chain management (SBSCM) problem is a multi-objective optimisation (MOO) problem since the objectives of each sustainability dimension and (or) each components under a same sustainability dimension can be conflicting. It is unlikely to have a single solution that could simultaneously satisfy all objectives. Therefore, achieving optimum for one objective requires compromise of other objectives. Several approaches have been developed to solve MOO problems. The simplest way reported from the academicians is to transform MOO problem into single objective optimisation (SOO) problem by converting all objectives into a similar form of objectives. However, converting environmental impacts into economic form might produce sub-optimal solution as the optimal result is highly dependent on the magnitude of the penalty cost. This paper presents a systematic approach which integrates both economic and environmental concerns in the supply chain by using the concept of analytic hierarchy process (AHP). Instead of merely focusing on carbon emission, this paper incorporates other environmental indicators as well, i. e., global warming potential (GWP), ozone depletion potential (ODP), acidification potential (AP), photochemical ozone creation potential (POCP), nutrification potential (NP), aquatic toxicity potential (ATP), terrestrial toxicity potential (TTP), abiotic depletion potential (ADP), water footprint and land footprint. On top of that, this paper also proposes a graphical illustration method to present the sustainability performance of the results. Both economic sustainability and environmental sustainability are expressed in a vector form. With the aid of this graphical representation, the tendency of the process towards each sustainability dimension can be clearly seen. A case study in Johor state is used to demonstrate the proposed method and a palm biomass supply chain with high sustainability performance (

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Using Electrospun Scaffolds to Promote Macrophage Phenotypic Modulation and Support Wound Healing
Authors: Hixon Katherine R. , Dunn Andrew J. , Flores Reynaldo , Minden-Birkenmaier Benjamin A. , Kalaf Emily A. Growney , Shornick Laurie P. , Sell Scott A. 
Published: July 2017

AbstractThe development of pressure ulcers in spinal cord injury patients is extremely common, often requiring extensive surgical procedures. Macrophages (MACs) play a crucial role in the innate immune system, contributing to wound healing and overall regeneration. MACs have been found to possess the potential to be activated by external factors from their M0 inactive state to an M1 proinflammatory or M2 regenerative state. This study conducted a comprehensive evaluation of MAC phenotype in response to electrospun scaffolds of varying material fiber/pore diameter, fiber stiffness, and +/− inclusion of platelet-rich plasma (PRP). Generally, itwas found that the addition of PRP resulted in decreased pore size, where 5 silk fibroin (SF) had the stiffest fibers. Furthermore, PRP scaffolds demonstrated an increased production of VEGF and chemotaxis. The polycaprolactone (PCL) and SF scaffolds had the largest cell infiltration and proliferation. Overall, it was found that 5% SF had both ideal fiber and pore structure, allowing for cell infiltration further enhanced by the presence of PRP. Additionally, this scaffold led to a reasonable production of VEGF while still allowing fibroblast proliferation to occur. These results suggest that such a scaffold could provide an off-the-shelf product capable of modifying the local MAC response.