bluuebunny/crossref_metadata_2025 huggingface dataset:
"Who Has Plots?"
Authors: Paine Drew , Lee Charlotte P.
Published: December 2017

Software is an integral element of the work of science yet it is not commonly an object of inquiry in studies of scientific infrastructures. This paper presents findings from an ethnographic study of a cosmology group's collaborative scientific software production. We demonstrate how these cosmologists use plots to simultaneously test their software and analyze data while interrogating multiple layers of infrastructural components. We broaden perspectives on scientific software development using a sociotechnical, software studies lens to examine this work of scientific discovery as a creative and embodied, yet exacting and methodical, activity that requires a 'human in the loop'. We offer a new reading of scientific software practices to convey how creating scientific software is often really the act of doing science itself--an intervention we believe is necessary to more successfully support scientific software sharing and infrastructure production.
Filtered Out
Authors: Porter John R. , Sobel Kiley , Fox Sarah E. , Bennett Cynthia L. , Kientz Julie A.
Published: December 2017

In this work, we sought to understand the experiences and disability disclosure preferences of adults with and without disabilities who have dated online. Our 91 survey respondents expressed varying opinions about the need for potential partners to disclose disability status when online dating depending on the nature or perceived severity, with "visible" disabilities carrying a higher expectation of upfront disclosure than "invisible" disabilities. Many disabled respondents also described proactively disclosing as a technique to filter potential connections. Our findings suggest that individuals with disabilities must perform additional labor and navigate complex group norms in pursuit of personal connection. We advocate that the social computing research community consider how these processes are driven by both societal expectation and the constraints of online dating platforms. We then offer design considerations and open questions as a means to extend social computing study at the intersection of online dating and disability studies.
Understanding Individual and Collaborative Problem-Solving with Patient-Generated Data
Authors: Raj Shriti , Newman Mark W. , Lee Joyce M. , Ackerman Mark S.
Published: December 2017

Making effective use of patient-generated data (PGD) is challenging for both patients and providers. Designing systems to support collaborative and individual use of PGD is a topic of importance in CSCW, considering the limitations of informatics tools. To inform better system design, we conducted a study including focus groups, observations and interviews with patients and providers to understand how PGD is interpreted and used. We found that while PGD is useful for identifying and solving disease-related problems, the following differences in patient-provider perceptions challenge its effective use - different perceptions about what is a problem, selecting what kinds of problems to focus on, and using different data representations. Drawing on these insights, we reflect on two specific conceptualizations of disease management behavior (sensemaking and problem-solving) as they relate to data specific activities of patients and providers and provide design suggestions for tools to support collaborative and individual use of PGD.
No Workflow Can Ever Be Enough
Authors: Retelny Daniela , Bernstein Michael S. , Valentine Melissa A.
Published: December 2017

The dominant crowdsourcing infrastructure today is the workflow, which decomposes goals into small independent tasks. However, complex goals such as design and engineering have remained stubbornly difficult to achieve with crowdsourcing workflows. Is this due to a lack of imagination, or a more fundamental limit? This paper explores this question through in-depth case studies of 22 workers across six workflow-based crowd teams, each pursuing a complex and interdependent web development goal. We used an inductive mixed method approach to analyze behavior trace data, chat logs, survey responses and work artifacts to understand how workers enacted and adapted the crowdsourcing workflows. Our results indicate that workflows served as useful coordination artifacts, but in many cases critically inhibited crowd workers from pursuing real-time adaptations to their work plans. However, the CSCW and organizational behavior literature argues that all sufficiently complex goals require open-ended adaptation. If complex work requires adaptation but traditional static crowdsourcing workflows can't support it, our results suggest that complex work may remain a fundamental limitation of workflow-based crowdsourcing infrastructures.
Social Media in Emergencies
Authors: Reuter Christian , Kaufhold Marc-André , Spielhofer Thomas , Hahne Anna Sophie
Published: December 2017

The value of social media in crises, disasters, and emergencies across different events (e.g. floods, storms, terroristic attacks), countries, and for heterogeneous participants (e.g. citizens, emergency services) is now well-attested. Existing work has examined the potentials and weaknesses of its use during specific events. Fewer studies, however, have focused on citizens' perceptions of social media in emergencies, and none have deployed a representative sample to examine this. We present the results of the first representative study on citizens' perception of social media in emergencies that we have conducted in Germany. Our study highlights, for example, that around half (45%) of people have used social media during an emergency to share and or look for information. In contrast, false rumours on social media (74%) are perceived as a threat. Moreover, only a minority of people have downloaded a smartphone app for emergencies (16%), with the most popular ones' weather and first aid apps.
WeBrowse
Authors: Scavo Giuseppe , Ben Houidi Zied , Traverso Stefano , Teixeira Renata , Mellia Marco
Published: December 2017

One of the limits of web content discovery tools, let them be recommender systems or content curation tools such as social rating, social bookmarking and other social media, is the scarcity of user input (e.g. rate, submit, share). This problem is even worse in the case of what we call communities of a place: people who study, live or work at the same place. Such people often share common interests but either do not know each other or fail to actively engage in submitting and relaying information. In this paper, we investigate the feasibility of using the aggregated clicks of entire communities of users to passively emulate a content curation service a la Reddit. To this end, we prototype and deploy WeBrowse, a content curation service based on the processing of raw HTTP logs. Evaluation based on our deployments demonstrates feasibility at scale while respecting user privacy. The majority of WeBrowse's users welcome the quality of content it promotes.
The Gig Economy and Information Infrastructure
Authors: Sutherland Will , Jarrahi Mohammad Hossein
Published: December 2017

Ongoing discussions of the gig economy have focused on the critical aspect of digital mediation, and in particular the role of applications and platforms such as Uber or TaskRabbit. We extend this discussion by considering more decentralized contexts of gig economy, in which individuals do not rely on a single dominant, central intermediary, but rather exercise a higher degree of agency in arranging and aligning multiple digital platforms to support relevant work practices.We employ the concept of information infrastructure to describe the emergent configuration of heterogeneous digital platforms leveraged by digital nomads as a community of location-independent, remote workers. Using both forum analysis and in-depth interviews, we examine how the digital nomad community dynamically brings together and negotiates digital mediation in the form of an information infrastructure.
Crowdcasting
Authors: Tang John , Venolia Gina , Inkpen Kori , Parker Charles , Gruen Robert , Pelton Alicia
Published: December 2017

We designed and developed a "crowdcasting" prototype to enable remote people to participate in a live event through a collection of live streams coming from the event. Viewers could select from a choice of streams and interact with the streamer and other viewers through text comments and heart reactions. We deployed the prototype in three live events: a Winterfest holiday festival, a local Women's March, and the South by Southwest festival. We found that viewers actively switched among a choice of streams from the event and actively interacted with each other, especially through text comments. Streams of walking about among exhibits or city sights elicited more user interaction than streams of lectures. We observed that voluntary viewers had a wider variation in how long they viewed the event, and switched among streams less and had less interaction through text comments compared to viewers recruited through Mechanical Turk.
Social CheatSheet
Authors: Vermette Laton , Dembla Shruti , Wang April Y. , McGrenere Joanna , Chilana Parmit K.
Published: December 2017

Users can often find it difficult to sift through dense help pages, tutorials, Q&A sites, blogs, and wikis to locate useful task-specific instructions for feature-rich applications. We present Social CheatSheet, an interactive information overlay that can appear atop any existing web application and retrieve relevant step-by-step instructions and tutorials curated by other users. Based on results of our formative study, the system offers several features for users to search, browse, filter, and bookmark community-generated help content and to ask questions and clarifications. Furthermore, Social CheatSheet includes embedded curation features for users to generate their own annotated notes and tutorials that can be kept private or shared with the user community. A weeklong deployment study with 15 users showed that users found Social CheatSheet to be useful and they were able to easily both add their own curated content and locate content generated by other users. The majority of users wanted to keep using the system beyond the deployment. We discuss the potential of Social CheatSheet as an application-independent platform driven by community curation efforts to lower the barriers in finding relevant help and instructions.
Eliciting Values Reflections by Engaging Privacy Futures Using Design Workbooks
Authors: Wong Richmond Y. , Mulligan Deirdre K. , Van Wyk Ellen , Pierce James , Chuang John
Published: December 2017

Although "privacy by design" (PBD)?embedding privacy protections into products during design, rather than retroactively?uses the term "design" to recognize how technical design choices implement and settle policy, design approaches and methodologies are largely absent from PBD conversations. Critical, speculative, and value-centered design approaches can be used to elicit reflections on relevant social values early in product development, and are a natural fit for PBD and necessary to achieve PBD's goal. Bringing these together, we present a case study using a design workbook of speculative design fictions as a values elicitation tool. Originally used as a reflective tool among a research group, we transformed the workbook into artifacts to share as values elicitation tools in interviews with graduate students training as future technology professionals. We discuss how these design artifacts surface contextual, socially-oriented understandings of privacy, and their potential utility in relationship to other values levers.
"Our Privacy Needs to be Protected at All Costs"
Authors: Xia Huichuan , Wang Yang , Huang Yun , Shah Anuj
Published: December 2017

Crowdsourcing platforms such as Amazon Mechanical Turk (MTurk) are widely used by organizations, researchers, and individuals to outsource a broad range of tasks to crowd workers. Prior research has shown that crowdsourcing can pose privacy risks (e.g., de-anonymization) to crowd workers. However, little is known about the specific privacy issues crowd workers have experienced and how they perceive the state of privacy in crowdsourcing. In this paper, we present results from an online survey of 435 MTurk crowd workers from the US, India, and other countries and areas. Our respondents reported different types of privacy concerns (e.g., data aggregation, profiling, scams), experiences of privacy losses (e.g., phishing, malware, stalking, targeted ads), and privacy expectations on MTurk (e.g., screening tasks). Respondents from multiple countries and areas reported experiences with the same privacy issues, suggesting that these problems may be endemic to the whole MTurk platform. We discuss challenges, high-level principles and concrete suggestions in protecting crowd workers'; privacy on MTurk and in crowdsourcing more broadly.
Crowd Development
Authors: Zhang Ark Fangzhou , Livneh Danielle , Budak Ceren , Robert Lionel P. , Romero Daniel M.
Published: December 2017

Collaborative crowdsourcing is an increasingly common way of accomplishing work in our economy. Yet, we know very little about how the behavior of these crowds changes over time and how these dynamics impact their performance. In this paper, we take a group development approach that considers how the behavior of crowds change over time in anticipation and as a result of their evaluation and recognition. Towards this goal, this paper studies the collaborative behavior of groups comprised of editors of articles that have been recognized for their outstanding quality and given the Good Articles (GA) status and those that eventually become Featured Articles (FA) on Wikipedia. The results show that the collaborative behavior of GA groups radically changes just prior to their nomination. In particular, the GA groups experience increases in the level of activity, centralization of workload, and level of GA experience and decreases in conflict (i.e., reverts) among editors. After being promoted to GA, they converge back to their typical behavior and composition. This indicates that crowd behavior prior to their evaluation period is dramatically different than behavior before or after. In addition, the collaborative behaviors of crowds during their promotion to GA are predictive of whether they are eventually promoted to FA. Our findings shed new light on the importance of time in understanding the relationship between crowd performance and collaborative measures such as centralization, conflict and experience.
The Effect of Computer-Generated Descriptions on Photo-Sharing Experiences of People with Visual Impairments
Authors: Zhao Yuhang , Wu Shaomei , Reynolds Lindsay , Azenkot Shiri
Published: December 2017

Like sighted people, visually impaired people want to share photographs on social networking services, but find it difficult to identify and select photos from their albums. We aimed to address this problem by incorporating state-of-the-art computer-generated descriptions into Facebook's photo-sharing feature. We interviewed 12 visually impaired participants to understand their photo-sharing experiences and designed a photo description feature for the Facebook mobile application. We evaluated this feature with six participants in a seven-day diary study. We found that participants used the descriptions to recall and organize their photos, but they hesitated to upload photos without a sighted person's input. In addition to basic information about photo content, participants wanted to know more details about salient objects and people, and whether the photos reflected their personal aesthetic. We discuss these findings from the lens of self-disclosure and self-presentation theories and propose new computer vision research directions that will better support visual content sharing by visually impaired people.
Drawing the Lines of Contention
Authors: Stewart Leo Graiden , Arif Ahmer , Nied A. Conrad , Spiro Emma S. , Starbird Kate
Published: December 2017

This research examines Twitter discourse related to #BlackLivesMatter and police-related shooting events in 2016 through a mixed-method, interpretative approach. We construct a "shared audience graph", revealing structural and ideological disparities between two groups of participants (one on the political left, the other on the political right). We utilize an integrated networked gatekeeping and framing lens to examine how #BlackLivesMatter frames were produced--and how they were
contested
--by separate communities of supporters and critics. Among other empirical findings, this work demonstrates hashtags being used in diverse ways--e.g. to mark participation, assert individual identity, promote group identity, and support or challenge a frame. Considered from a networked gatekeeping perspective, we illustrate how hashtags can serve as channeling mechanisms, shaping trajectories of information flow. This analysis also reveals a right-leaning community of BlackLivesMatter critics to have a more well-defined group of crowdsourced elite who largely define their side's counter-frame.
When Distribution of Tasks and Skills are Fundamentally Problematic
Authors: Matthiesen Stina , Bjørn Pernille
Published: December 2017

Using ethnographic data, we provide a critical reflection on the discrepancies between the application of agile development principles and the conditions which render these principles effective for global software development work. This reflection is based on the analysis of a failed collaboration within a global software project, which relied heavily on feedback from mundane project tools utilized for everyday coordination and monitoring. Our study reveals that these tools hid serious issues relating to both the distribution of socio-technical skills and a discharge of accountability in task execution. As a result, markers of complex collaborative problems were concealed. Furthermore, the imbalance evident in outsourcing setups, which is enacted through high and low status task distribution among partners, further compounds collaboration problems by emphasizing assumptions about remote workers in the absence of direct forms of knowledge interchange.
xPress
Authors: Brewer Robin N. , Piper Anne Marie
Published: December 2017

Although many older adults are active online, certain age-related disabilities, such as late-life vision impairment, make sustaining online participation difficult. Motivated by the need for accessible online spaces for people experiencing vision impairment in older adulthood, we developed xPress, a voice-based online blogging community. Through a 10-week deployment with seven older adults with acquired vision loss, we analyze how this type of online community enables connecting with peers, sharing experiences, and offering social support in new ways. The design of xPress also highlights the importance of human voice in accessible social platforms and reveals expectations around community participation. We discuss designing for age and disability through the lens of intersectionality and offer design considerations for similar voice-based online communities.
Improving the Efficiency of GPGPU Work-Queue Through Data Awareness
Authors: Huang Libo , Lü Yashuai , Shen Li , Wang Zhiying
Published: December 2017

The architecture and programming model of current GPGPUs are best suited for applications that are dominated by structured control and data flows across large regular datasets. Parallel workloads with irregular control and data structures cannot easily harness the processing power of the GPGPU. One approach for mapping these irregular-parallel workloads to GPGPUs is using work-queues. The work-queue approach improves the utilization of SIMD units by only processing useful works that are dynamically generated during execution. As current GPGPUs lack necessary supports for work-queues, a software-based work-queue implementation often suffers from memory contention and load balancing issues. In this article, we present a novel hardware work-queue design named
DaQueue
, which incorporates three data-aware features to improve the efficiency of work-queues on GPGPUs. We evaluate our proposal on the irregular-parallel workloads and carry out a case study on a path tracing pipeline with a cycle-level simulator. Experimental results show that for the tested workloads, DaQueue improves performance by 1.53× on average and up to 1.91×. Compared to a hardware worklist approach that is the state-of-the-art prior work, DaQueue can achieve an average of 33.92% extra speedup with less hardware area cost.
Carbon monoxide in lung cell physiology and disease
Authors: Ryter Stefan W. , Ma Kevin C. , Choi Augustine M. K.
Published: December 2017

Carbon monoxide (CO) is an endogenously produced gas that has gained recognition as a biological signal transduction effector with properties similar, but not identical, to that of nitric oxide (NO). CO, which binds primarily to heme iron, may activate the hemoprotein guanylate cyclase, although with lower potency than NO. Furthermore, CO can modulate the activities of several cellular signaling molecules such as p38 MAPK, ERK1/2, JNK, Akt, NF-κB, and others. Emerging studies suggest that mitochondria, the energy-generating organelle of cells, represent a key target of CO action in eukaryotes. Dose-dependent modulation of mitochondrial function by CO can result in alteration of mitochondrial membrane potential, mitochondrial reactive oxygen species production, release of proapoptotic and proinflammatory mediators, as well as the inhibition of respiration at high concentration. CO, through modulation of signaling pathways, can impact key biological processes including autophagy, mitochondrial biogenesis, programmed cell death (apoptosis), cellular proliferation, inflammation, and innate immune responses. Inhaled CO is widely known as an inhalation hazard due to its rapid complexation with hemoglobin, resulting in impaired oxygen delivery to tissues and hypoxemia. Despite systemic and cellular toxicity at high concentrations, CO has demonstrated cyto- and tissue-protective effects at low concentration in animal models of organ injury and disease. These include models of acute lung injury (e.g., hyperoxia, hypoxia, ischemia-reperfusion, mechanical ventilation, bleomycin) and sepsis. The success of CO as a candidate therapeutic in preclinical models suggests potential clinical application in inflammatory and proliferative disorders, which is currently under evaluation in clinical trials.
Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells
Authors: Petrova Rosica S. , Webb Kevin F. , Vaghefi Ehsan , Walker Kerry , Schey Kevin L. , Donaldson Paul J.
Published: December 2017

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.
lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214
Authors: Huang Xinli , Gao Yun , Qin Jianjie , Lu Sen
Published: December 2017

The aberrant expression of long noncoding RNAs (lncRNAs) has been involved in various human tumors including hepatocellular carcinoma (HCC). Our study aimed to investigate the potential molecular mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in HCC. The expression of MIAT and micro-RNA (miR)-214 in HCC tissues and cells was examined by quantitative real-time PCR, and the levels of enhancer of zeste homolog 2 (EZH2) and β-catenin were detected by Western blot assay. Immunoprecipitation analysis was used to detect the level of H3/H4 histone acetylation. RNA pull-down assay was performed to confirm the targeting regulatory relationship between miR-214 and MIAT. Cell viability, proliferation, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), [3H]thymidine incorporation, and Transwell assays, respectively. BALB/c nude mice were used to establish a hepatocellular carcinoma animal model with subcutaneous injection of SK-HEP-1 cells. Upregulation of MIAT is related to the proliferation and invasion of HCC, and downregulating MIAT expression inhibited HCC cell proliferation and invasion. The H3/H4 histone acetylation level of MIAT promoter in HCC tissues was higher than that in normal tissues. MIAT negatively regulated miR-214 in HCC cells. Inhibition of miR-214 reversed the influence of MIAT downregulation on HCC cell proliferation and invasion. In nude mouse xenograft models, downregulation of MIAT markedly suppressed the tumor growth of HCC via releasing miR-214. In conclusion, lncRNA MIAT promotes the proliferation and invasion of HCC cells through sponging miR-214, which brings a novel target for the therapy and prognosis of hepatocellular carcinoma.

NEW & NOTEWORTHY This is the first research showing long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) to have a regulatory effect on hepatocellular carcinoma. Micro-RNA (miR)-214 could be sponged by MIAT to promote the proliferation and invasion of hepatocellular carcinoma cells. The lncRNA MIAT/miR-214 axis brings a novel insight for the therapy and prognosis of hepatocellular carcinoma.
Flaxseed: its bioactive components and their cardiovascular benefits
Authors: Parikh Mihir , Netticadan Thomas , Pierce Grant N.
Published: December 2017

Cardiovascular disease remains the leading cause of mortality and morbidity worldwide. The inclusion of functional foods and natural health products in the diet are gaining increasing recognition as integral components of lifestyle changes in the fight against cardiovascular disease. Several preclinical and clinical studies have shown the beneficial cardiovascular effects of dietary supplementation with flaxseed. The cardiovascular effects of dietary flaxseed have included an antihypertensive action, antiatherogenic effects, a lowering of cholesterol, an anti-inflammatory action, and an inhibition of arrhythmias. Its enrichment in the ω-3 fatty acid α-linolenic acid and the antioxidant lignan secoisolariciresinol diglucoside as well as its high fiber content have been implicated primarily in these beneficial cardiovascular actions. Although not as well recognized, flaxseed is also composed of other potential bioactive compounds such as proteins, cyclolinopeptides, and cyanogenic glycosides, which may also produce biological actions. These compounds could also be responsible for the cardiovascular effects of flaxseed. This article will not only summarize the cardiovascular effects of dietary supplementation with flaxseed but also review its bioactive compounds in terms of their properties, biological effects, and proposed mechanisms of action. It will also discuss promising research directions for the future to identify additional health-related benefits of dietary flaxseed.
Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?
Authors: Woessner Mary N. , McIlvenna Luke C. , Ortiz de Zevallos Joaquin , Neil Christopher J. , Allen Jason D.
Published: December 2017

Oral consumption of inorganic nitrate, which is abundant in green leafy vegetables and roots, has been shown to increase circulating plasma nitrite concentration, which can be converted to nitric oxide in low oxygen conditions. The associated beneficial physiological effects include a reduction in blood pressure, modification of platelet aggregation, and increases in limb blood flow. There have been numerous studies of nitrate supplementation in healthy recreational and competitive athletes; however, the ergogenic benefits are currently unclear due to a variety of factors including small sample sizes, different dosing regimens, variable nitrate conversion rates, the heterogeneity of participants’ initial fitness levels, and the types of exercise tests used. In clinical populations, the study results seem more promising, particularly in patients with cardiovascular diseases who typically present with disruptions in the ability to transport oxygen from the atmosphere to working tissues and reduced exercise tolerance. Many of these disease-related, physiological maladaptations, including endothelial dysfunction, increased reactive oxygen species, reduced tissue perfusion, and muscle mitochondrial dysfunction, have been previously identified as potential targets for nitric oxide restorative effects. This review is the first of its kind to outline the current evidence for inorganic nitrate supplementation as a therapeutic intervention to restore exercise tolerance and improve quality of life in patients with cardiovascular diseases. We summarize the factors that appear to limit or maximize its effectiveness and present a case for why it may be more effective in patients with cardiovascular disease than as ergogenic aid in healthy populations.
Reduced longitudinal contraction is associated with ischemic mitral regurgitation after posterior MI
Authors: Ishikawa Kiyotake , Watanabe Shin , Hammoudi Nadjib , Aguero Jaume , Bikou Olympia , Fish Kenneth , Hajjar Roger J.
Published: December 2017

The role of left ventricular (LV) longitudinal contraction in ischemic mitral regurgitation (MR) remains unclear. We hypothesized that reduced longitudinal contraction disrupts normal mitral valve plane displacement during systole and leads to mitral valve tethering, thereby inducing ischemic MR. Twenty-three Yorkshire pigs underwent induction of different-sized posterior myocardial infarction (MI) using a percutaneous approach. The incidence of MR and its association with LV longitudinal strain were examined using speckle-tracking echocardiography at 1 mo post-MI to determine their relationship. A total of 17 pigs survived MI and completed the study. Pigs developed no more than mild MR after proximal left circumflex artery (LCx) occlusion (LCx group; n = 7). Addition of a first diagonal branch (D1) occlusion to LCx-MI (LCx + D1 group; n = 7) resulted in moderate to severe MR development 1 mo post-MI. LCx + D1 animals had lower longitudinal strain compared with the LCx group, whereas circumferential strain and LV rotation did not differ significantly. Posterolateral annular displacement toward the apex was significantly reduced in LCx + D1 animals, whereas the septal annular displacement was similar, suggesting an asymmetric mitral annular plane excursion in the LCx + D1 group. To exclude the contribution of papillary muscle infarction in MR development in our model, three pigs underwent obtuse marginal branch + D1 occlusion. None of these pigs developed significant MR after 1 mo. In conclusion, reduced longitudinal contraction contributes to the development of ischemic MR in a large posterior MI.

NEW & NOTEWORTHY In this study, using our unique swine models of different-sized myocardial infarction, we showed, for the first time, that reduced longitudinal contraction contributes to the development of ischemic mitral regurgitation in a large posterior myocardial infarction. Our study adds new insights into the mechanisms of ischemic mitral regurgitation pathophysiology.
Differential effects of alcohol and its metabolite acetaldehyde on vascular smooth muscle cell Notch signaling and growth
Authors: Hatch Ekaterina , Morrow David , Liu Weimin , Cahill Paul A. , Redmond Eileen M.
Published: December 2017

Alcohol (EtOH) consumption can variously affect cardiovascular disease. Our aim was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT) on vascular smooth muscle Notch signaling and cell growth, which are important for atherogenesis. Human coronary artery smooth muscle cells (HCASMCs) were treated with EtOH (25 mM) or ACT (10 or 25 μM). As previously reported, EtOH inhibited Notch signaling and growth of HCASMCs. In contrast, ACT treatment stimulated HCASMC proliferation (cell counts) and increased proliferating cell nuclear antigen expression, concomitant with stimulation of Notch signaling, as determined by increased Notch receptor (N1 and N3) and target gene (Hairy-related transcription factor 1–3) mRNA levels. Interaction of the ligand with the Notch receptor initiates proteolytic cleavage by α- and γ-secretase, resulting in the release of the active Notch intracellular domain. Neither EtOH nor ACT had any significant effect on α-secretase activity. A fluorogenic peptide cleavage assay demonstrated almost complete inhibition by EtOH of Delta-like ligand 4-stimulated γ-secretase activity in solubilized HCASMCs (similar to the effect of the control inhibitor DAPT) but no effect of ACT treatment. EtOH, but not ACT, affected the association and distribution of the γ-secretase catalytic subunit presenilin-1 with lipid rafts, as determined by dual fluorescent labeling and confocal microscopic visualization. In conclusion, ACT stimulates vascular smooth muscle cell Notch signaling and growth, effects opposite to those of EtOH. These differential actions on vascular smooth muscle cells of EtOH and its metabolite ACT may be important in mediating the ultimate effects of drinking on cardiovascular disease.

NEW & NOTEWORTHY Acetaldehyde stimulates, in a Notch-dependent manner, the vascular smooth muscle cell growth that contributes to atherogenesis; effects opposite to those of ethanol. These data suggest that in addition to ethanol itself, its metabolite acetaldehyde may also mediate some of the effects of alcohol consumption on vascular cells and, thus, cardiovascular health.
Roles of high-mobility group box 1 and thrombin in murine pulmonary fibrosis and the therapeutic potential of thrombomodulin
Authors: Kida Takashi , Seno Takahiro , Nagahara Hidetake , Inoue Takuya , Nakabayashi Amane , Kukida Yuji , Fujioka Kazuki , Fujii Wataru , Wada Makoto , Kohno Masataka , Kawahito Yutaka
Published: December 2017

Cross talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1), and thrombin and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal instillation of bleomycin. We first assessed HMGB1, thrombin, transforming growth factor (TGF)-β1, and α-smooth muscle actin (SMA) levels in bronchoalveolar lavage fluid and lung tissue sections over time. Expression of HMGB1 and thrombin was elevated before that of TGF-β1 and α-SMA and remained high during the fibrotic phase after bleomycin instillation. We next examined whether in vitro stimulation with HMGB1 and thrombin induced expression of TGF-β1 and α-SMA in cultured alveolar macrophages and lung fibroblasts, respectively, by performing quantitative PCR, enzyme-linked immunosorbent assay, Western blot, and immunofluorescence analyses. HMGB1 and thrombin stimulation induced TGF-β1 production by alveolar macrophages, and thrombin stimulation also induced α-SMA expression in lung fibroblasts. Finally, we evaluated the effect of rhTM on bleomycin-induced pulmonary fibrosis. Compared with the vehicle control, both early and late-phase administration of rhTM suppressed the fibrotic process. Our results suggest that HMGB1 and thrombin were involved in the pathophysiology of pulmonary fibrosis via production of profibrotic proteins and that rhTM attenuated bleomycin-induced pulmonary fibrosis. rhTM may be a therapeutic option for acute or subacute pulmonary fibrosis.
Animal models of preeclampsia: translational failings and why
Authors: Marshall Sarah A. , Hannan Natalie J. , Jelinic Maria , Nguyen Thy P.H. , Girling Jane E. , Parry Laura J.
Published: December 2017

Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of both maternal and fetal morbidity and mortality. Our current understanding of the cause(s) of preeclampsia is far from complete, and the lack of a single reliable animal model that recapitulates all aspects of the disease further confounds our understanding. This is partially due to the heterogeneous nature of the disease, coupled with our evolving understanding of its etiology. Nevertheless, animal models are still highly relevant and useful tools that help us better understand the pathophysiology of specific aspects of preeclampsia. This review summarizes the various types and characteristics of animal models used to study preeclampsia, highlighting particular features of these models relevant to clinical translation. This review points out the strengths and limitations of these models to illustrate the importance of using the appropriate model depending on the research question.
BDNF overexpression in the bladder induces neuronal changes to mediate bladder overactivity
Authors: Kashyap Mahendra P. , Pore Subrata K. , de Groat William C. , Chermansky Christopher J. , Yoshimura Naoki , Tyagi Pradeep
Published: December 2017

Elevated levels of brain-derived neurotrophic factor (BDNF) in urine of overactive bladder (OAB) patients support the association of BDNF with OAB symptoms, but the causality is not known. Here, we investigated the functionality of BDNF overexpression in rat bladder following bladder wall transfection of either BDNF or luciferase (luciferase) transgenes (10 µg). One week after transfection, BDNF overexpression in bladder tissue and elevation of urine BDNF levels were observed together with increased transcript of BDNF, its cognate receptors (TrkB and p75NTR), and downstream PLCγ isoforms in bladder. BDNF overexpression can induce the bladder overactivity (BO) phenotype which is demonstrated by the increased voiding pressure and reduced intercontractile interval during transurethral open cystometry under urethane anesthesia. A role for BDNF-mediated enhancement of prejunctional cholinergic transmission in BO is supported by the significant increase in the atropine- and neostigmine-sensitive component of nerve-evoked contractions and upregulation of choline acetyltransferase, vesicular acetylcholine transporter, and transporter Oct2 and -α1 receptors. In addition, higher expression of transient receptor channels (TRPV1 and TRPA1) and pannexin-1 channels in conjunction with elevation of ATP and neurotrophins in bladder and also in L6/S1 dorsal root ganglia together support a role for sensitized afferent nerve terminals in BO. Overall, genomic changes in efferent and afferent neurons of bladder induced by the overexpression of BDNF per se establish a mechanistic link between elevated BDNF levels in urine and dysfunctional voiding observed in animal models and in OAB patients.
Metformin: an antiproliferative agent and methylation regulator in treating prostatic disease?
Authors: Wang Zongwei , Olumi Aria F.
Published: December 2017

Existing drugs that have been used in clinical practice for other purposes can prove useful for reutilization, since much of the safety profile and pharmacokinetics have been completed. Therefore, the drugs can enter clinical practice for a variety of causes with less regulatory burden. Metformin may prove to be such a drug; it may have a role in other diseases, besides the management of diabetes. In this perspective, we provide our findings and understanding of metformin as an alternative way to treat urological abnormal proliferation. We propose the potential mechanisms into two hallmarks: direct antiproliferative function via insulin-like growth factor (IGF) signaling pathway and epigenetic modulating via adjusting DNA methylation. These specific hallmarks may ultimately contribute to a better understanding of metformin in treating prostatic diseases.
Influence of age and gender on the phase and strength of the relation between heart period and systolic blood pressure spontaneous fluctuations
Authors: Milan-Mattos Juliana C. , Porta Alberto , Perseguini Natália M. , Minatel Vinicius , Rehder-Santos Patricia , Takahashi Anielle C. M. , Mattiello Stela M. , Catai Aparecida M.
Published: December 2017

Aging affects baroreflex regulation. The effect of senescence on baroreflex control was assessed from spontaneous fluctuations of heart period (HP) and systolic arterial pressure (SAP) through the HP-SAP gain, while the HP-SAP phase and strength are usually disregarded. This study checks whether the HP-SAP phase and strength, as estimated, respectively, via the phase of the HP-SAP cross spectrum (PhHP-SAP) and squared coherence function (K2HP-SAP), vary with age in healthy individuals and trends are gender-dependent. We evaluated 110 healthy volunteers (55 males) divided into five age subgroups (21–30, 31–40, 41–50, 51–60, and 61–70 yr). Each subgroup was formed by 22 subjects (11 males). HP series was extracted from electrocardiogram and SAP from finger arterial pressure at supine resting (REST) and during active standing (STAND). PhHP-SAP and K2HP-SAP functions were sampled in low-frequency (LF, from 0.04 to 0.15 Hz) and in high-frequency (HF, above 0.15 Hz) bands. Both at REST and during STAND PhHP-SAP(LF) showed a negative correlation with age regardless of gender even though values were more negative in women. This trend was shown to be compatible with a progressive increase of the baroreflex latency with age. At REST K2HP-SAP(LF) decreased with age regardless of gender, but during STAND the high values of K2HP-SAP(LF) were more preserved in men than women. At REST and during STAND the association of PhHP-SAP(HF) and K2HP-SAP(HF) with age was absent. The findings points to a greater instability of baroreflex control with age that seems to affect to a greater extent women than men.

NEW & NOTEWORTHY Aging increases cardiac baroreflex latency and decreases the degree of cardiac baroreflex involvement in regulating cardiovascular variables. These trends are gender independent but lead to longer delays and asmaller degree of cardiac baroreflex involvement in women than in men, especially during active standing, with important implications on the tolerance to an orthostatic stressor.
Task dependence of odor discrimination: choosing between speed and accuracy
Authors: Brooks Jack , Nicholas Jennifer , Robertson Jennifer J.
Published: December 2017

Odor discrimination is a complex task that may be improved by increasing sampling time to facilitate evidence accumulation. However, experiments testing this phenomenon in olfaction have produced conflicting results. To resolve this disparity, Frederick et al. (Frederick DE, Brown A, Tacopina S, Mehta N, Vujovic M, Brim E, Amina T, Fixsen B, Kay LM. J Neurosci 37: 4416–4426, 2017) conducted experiments that suggest that sampling time and performance are task dependent. Their findings have implications for understanding olfactory processing and experimental design, specifically the effect of subtle differences in experimental design on study results.
Association of complement receptor 1 gene polymorphisms with cognitive function
Authors: Zijlstra L. E. , Jukema J. W. , Mooijaart S. P. , de Vries M. A. , Stott D. J. , Castro Cabezas M. , Trompet S.
Published: December 2017

Previous evidence suggest involvement of the complement receptor 1 (CR1) in development of Alzheimer’s disease. We investigated the association of CR1 gene polymorphisms with cognitive function in older subjects. Single nucleotide polymorphisms (SNPs) within the CR1 region on chromosome 1 ( n = 73) were assessed in 5,244 participants in the PROspective Study of Pravastatin in the Elderly at Risk (51.9% female, mean age 75.3 yr). Linear regression, adjusted for age, sex, country, and use of pravastatin, was used to assess the association between the SNPs and cognitive function. All 73 SNPs within the genomic region of the CR1 gene on chromosome 1 were extracted. Eighteen were independent, according to a relatively stringent R2 threshold of >0.8 with LDlink. Twelve of the 18 investigated CR1 SNPs were significantly associated with a decline in cognitive function (all P < 0.05). These data indicate that genetic variation within the CR1 gene is associated not only with Alzheimer’s disease, but also with general cognitive function during late life.
The Hypoactivity Associated with the Repeated Exposure to Atrazine Is Related to Decreases in the Specific Binding to D1-DA Receptors in the Striatum of Rats
Authors: Márquez-Ramos José Abraham , Hernández-Plata Isela , Díaz-Muñoz Mauricio , Rodríguez Verónica M.
Published: December 2017

The herbicide atrazine (ATR) has a potential toxic effect on the neuronal circuits of the brain, specifically on two major dopaminergic pathways: the nigrostriatal and mesolimbic circuits. In this work, we repeatedly exposed adult male Sprague-Dawley rats to 6 injections of 100 mg ATR/kg of body weight (for two weeks) and one saline injection two days after ATR administration. Locomotor activity was assessed for 15 minutes and/or 2 hours after ATR or saline injection and 2 months after the final ATR administration. The specific binding of [3H]-SCH23390 to D1-DA receptors and that of [3H]-Spiperone to D2-DA receptors in the dorsal and ventral striatum were assessed 2 days and 2 months after ATR treatment. ATR administration resulted in immediate, short- and long-term hypoactivity and reduced specific binding of [3H]-SCH23390 in the dorsal striatum of rats evaluated 2 months after the last ATR injection. The specific binding of [3H]-SCH23390 in the ventral striatum and the specific binding of [3H]-Spiperone in the dorsal and ventral striatum remained unchanged at 2 days or 2 months after ATR treatment. These results, together with previous findings of our group, indicate that the nigrostriatal system is a preferential target for ATR exposure.