bluuebunny/crossref_metadata_2025 huggingface dataset:
The Frequency of Vaccine-Induced T-Cell Responses Does Not Predict the Rate of Acquisition after Repeated Intrarectal SIVmac239 Challenges in

Mamu-B*08
+

Rhesus Macaques
Authors: Martins Mauricio A. , Gonzalez-Nieto Lucas , Shin Young C. , Domingues Aline , Gutman Martin J. , Maxwell Helen S. , Magnani Diogo M. , Ricciardi Michael J. , Pedreño-Lopez Núria , Bailey Varian K. , Altman John D. , Parks Christopher L. , Allison David B. , Ejima Keisuke , Rakasz Eva G. , Capuano Saverio , Desrosiers Ronald C. , Lifson Jeffrey D. , Watkins David I.
Published: December 2018

It is generally accepted that the antiviral effects of vaccine-induced classical CD8
+
T-cell responses against human immunodeficiency virus (HIV) are limited to partial reductions in viremia after the establishment of productive infection. Here we show that rhesus macaques (RMs) vaccinated with Vif and Nef acquired simian immunodeficiency virus (SIV) infection at a lower (albeit not statistically significant) rate than control RMs following repeated intrarectal challenges with a pathogenic SIV clone. All animals in the present experiment expressed the elite control-associated major histocompatibility complex class I (MHC-I) molecule Mamu-B*08 that binds immunodominant epitopes in Vif and Nef. Though preliminary, these results provide tantalizing evidence that the protective efficacy of vaccine-elicited CD8
+
T cells may be greater than previously thought. Future studies should examine if vaccine-induced cellular immunity can prevent systemic viral replication in RMs that do not express MHC-I alleles associated with elite control of SIV infection.
The Potato Virus X TGBp2 Protein Plays Dual Functional Roles in Viral Replication and Movement
Authors: Wu Xiaoyun , Liu Jiahui , Chai Mengzhu , Wang Jinhui , Li Dalong , Wang Aiming , Cheng Xiaofei
Published: December 2018

Many plant viruses contain three partially overlapping open reading frames (ORFs), termed the triple gene block (TGB), for intercellular movement. However, how the corresponding three proteins coordinate their functions remains obscure. In the present study, we provided multiple lines of evidence supporting the notion that PVX TGBp2 functions as the molecular adaptor bridging the interaction between the RdRp/dsRNA body and TGBp3 by forming “chain mail”-like structures in the RdRp/dsRNA body, which can also enhance viral replication. Taken together, our results provide new insights into the replication and movement of PVX and possibly also other TGB-containing plant viruses.
Contrasting Roles of the PD-1 Signaling Pathway in Dendritic Cell-Mediated Induction and Regulation of HIV-1-Specific Effector T Cell Functions
Authors: Garcia-Bates Tatiana M. , Palma Mariana L. , Shen Chengli , Gambotto Andrea , Macatangay Bernard J. C. , Ferris Robert L. , Rinaldo Charles R. , Mailliard Robbie B.
Published: December 2018

Targeting the PD-1/PD-L1 immune checkpoint axis with signaling inhibitors has proven to be a powerful immunotherapeutic strategy to enhance the functional quality and survival of existing antigen-specific effector T cells. However, our study demonstrates that the context and timing of PD-1 signaling in T cells greatly impact the outcome of the effector response. In particular, we show that PD-1 activation plays a positive role during the DC-mediated initiation stage of the primary T cell response, while it serves as an inhibitory mechanism during the effector phase of the response. Therefore, caution should be taken in the design of therapies that include targeting of the PD-1/PD-L1 signaling pathway in order to avoid potential negative impacts on the induction of
de novo
T cell responses.
Human Norovirus Neutralized by a Monoclonal Antibody Targeting the Histo-Blood Group Antigen Pocket
Authors: Koromyslova Anna D. , Morozov Vasily A. , Hefele Lisa , Hansman Grant S.
Published: December 2018

The emergence of new epidemic GII.4 norovirus variants is thought to be associated with changes in antigenicity and HBGA binding capacity. Here, we show that HBGA binding profiles remain unchanged between the 1974 and 2012 GII.4 variants, whereas these variants showed various levels of reactivity against a panel of GII.4 MAbs. We identified a MAb that bound at the HBGA pocket, blocked norovirus VLPs from binding to HBGAs, and neutralized norovirus virions in the cell culture system. Raised against a GII.4 2006 strain, this MAb was unreactive to a GII.4 1974 isolate but was able to neutralize the newer 2012 strain, which has important implications for vaccine design. Altogether, these new findings suggest that the amino acid variations surrounding the HBGA pocket lead to temporal changes in antigenicity without affecting the ability of GII.4 variants to bind HBGAs, which are known cofactors for infection.
Identification of a Divergent Avian Influenza H3N2 Virus from Domestic Ducks in France
Authors: Briand François-Xavier , Niqueux Eric , Schmitz Audrey , Beven Veronique , Lucas Pierrick , Allée Chantal , Chatel Marina , Touzain Fabrice , Blanchard Yannick , Eterradossi Nicolas
Published: December 2018

An avian influenza H3N2 virus was isolated from domestic ducks in France in 2016. Although this French H3N2 virus possesses traits of an avian virus, the genetic distances observed for hemagglutinin (HA) and neuraminidase (NA) show that these two genes most likely evolved independently from other avian influenza sequences.
Complete Genome Sequence of H1N1 Swine Influenza Virus from Pigs in the Republic of Korea in 2016
Authors: Lee Ju-Yeon , Ouh In-Ohk , Cho Soo-Dong , Cho In-Soo , Park Choi Kyu , Song Jae-Young
Published: December 2018

We report here the genome sequence of the influenza A virus strain A/swine/Korea/61/2016, isolated from swine in the Republic of Korea. On the basis of sequence analysis, A/swine/Korea/61/2016 is marked from swine H1N1 influenza virus.
Draft Genome Sequence of Lactococcus lactis subsp. lactis W8, a Potential Nisin-Producing Starter Culture for Indian Traditional Fermented Milk (Dahi)
Authors: Mitra Suranjita , Mukhopadhyay Bidhan Chandra , Kazi Tawsif Ahmed , Bhattacharya Rajarshi , Mandal Sukhendu , Biswas Swadesh Ranjan
Published: December 2018

Dahi is a traditional Indian fermented milk consumed regularly as part of the diet because of its palatability and health benefits. Here, we report the draft genome sequence of a unique strain of
Lactococcus lactis
subsp.
Draft Genome Sequence of French Guiana
Leishmania
(
Viannia
)
guyanensis
Strain 204-365, Assembled Using Long Reads
Authors: Batra Dhwani , Lin Wuling , Rowe Lori A. , Sheth Mili , Zheng Yueli , Loparev Vladimir , de Almeida Marcos
Published: December 2018

We present here the draft genome sequence for
Leishmania (
Viannia)
guyanensis
. The isolate was obtained from a clinical case of cutaneous leishmaniasis in French Guiana.
Long-Read-Based Genome Sequences of Pandemic and Environmental Vibrio cholerae Strains
Authors: Matthey Noémie , Drebes Dörr Natália C. , Blokesch Melanie
Published: December 2018

The bacterium
Vibrio cholerae
exhibits two distinct lifestyles, one as an aquatic bacterium and the other as the etiological agent of the pandemic human disease cholera. Here, we report closed genome sequences of two seventh pandemic
V. cholerae
O1 El Tor strains, A1552 and N16961, and the environmental strain Sa5Y.
Revisiting the decoupling effects in the running of the Cosmological Constant
Authors: Antipin Oleg , Melić Blaženka
Published: December 2018

We revisit the decoupling effects associated with heavy particles in the renormalization group running of the vacuum energy in a mass-dependent renormalization scheme. We find the running of the vacuum energy stemming from the Higgs condensate in the entire energy range and show that it behaves as expected from the simple dimensional arguments, meaning that it exhibits the quadratic sensitivity to the mass of the heavy particles in the infrared regime. The consequence of such a running to the fine-tuning problem with the measured value of the Cosmological Constant is analyzed and the constraint on the mass spectrum of a given model is derived. We show that in the Standard Model (SM) this fine-tuning constraint is not satisfied while in the massless theories this constraint formally coincides with the well-known Veltman condition. We also provide a remarkably simple extension of the SM where saturation of this constraint enables us to predict the radiative Higgs mass correctly. Generalization to constant curvature spaces is also given.
Sasaki–Ricci flow on Sasaki–Einstein space T1,1 and deformations
Authors: Visinescu Mihai
Published: December 2018

We study the transverse Kähler structure of the Sasaki–Einstein space [Formula: see text]. A set of local holomorphic coordinates is introduced and a Sasakian analogue of the Kähler potential is given. We investigate deformations of the Sasaki–Einstein structure preserving the Reeb vector field, but modifying the contact form. For this kind of deformations, we consider the Sasaki–Ricci flow which converges in a suitable sense to a Sasaki–Ricci soliton. Finally, it is described the constructions of Hamiltonian holomorphic vector fields and Hamiltonian function on the [Formula: see text] manifold.
Novel guide star optimal selection algorithm for star sensors based on star clustering
Authors: Wu Feng , Zhu Xifang , Xiang Ruxi , Yu Qiuyang , Huang Tingting , Xu Qingquan , Li Hui
Published: December 2018

Modern space vehicles face the challenges to obtain more and more accurate attitudes in order to complete the demanding tasks. Onboard star sensors which identify the observed stars in the field of view according to the loaded guide star catalog and output accurate attitude have attracted most interests. Guide stars are usually required to distribute uniformly on the celestial sphere to improve the performance of the star pattern identification. An optimal selection algorithm is proposed to achieve an even distribution of guide stars in this paper. Constellation features are discussed. The mean shift algorithm is analyzed. The idea that distributes stars in the local field of view to constellations is proposed by using the star pair angular separations according to the star positions in the inertial coordinate system. The optimal selection algorithm of guide stars based on star clustering is developed. Its detailed implement procedures are introduced completely. The guide star optimal selection experiment in visible band by using SAO star catalog as the original star data is implemented. It proves that the proposed algorithm has the virtue of simple calculation and easy realization. The obtained guide star distribution is superior to the regression selection algorithm and the magnitude weighted method.
NSGA-II applied to dynamic flexible job shop scheduling problems with machine breakdown
Authors: Chen Chao , Ji Zhicheng , Wang Yan
Published: December 2018

This paper focuses on multi-objective dynamic flexible job shop scheduling problem (MODFJSP) with machine breakdown. First, a multi-objective dynamic scheduling model is established, with objectives to minimize makespan and total machine workload. Second, according to the processing status of faulty machine, a hybrid rescheduling strategy including transfer rescheduling strategy and complete rescheduling strategy is proposed to react to stochastic machine breakdown. The performance of two rescheduling strategies is analyzed in terms of the scheduling efficiency and its stability, from the delay extent and initial scheduling deviation, respectively. Besides, the optimal adaptation conditions of both scheduling strategies are obtained. Furthermore, the non-dominated sorting genetic algorithm (NSGA-II) is employed to solve the constructed model. Experimental results demonstrate the effectiveness of the proposed strategies on reducing the impact of machine breakdown in real scheduling.
Research on surface roughness prediction method based on composite penalty regression model
Authors: Ding Dong , Ji Zhicheng , Wang Yan
Published: December 2018

With the development of manufacturing technology, traditional empirical formulas are hard to deal with the relationships between complex manufacturing techniques and surface roughness. Current data fitting-based modeling methods often do not consider the influence of various factors on surface roughness and lack data cleaning capability. This paper proposes a method to reduce the dimension of data features, which includes the Lasso model to determine the correlation degree of processing parameters and roughness, and solves the possible sparse coefficient relationship between processing parameters and roughness. The ridge regression is also introduced to predict the workpiece surface roughness. The results show that compared with the existing prediction model, this prediction method has high accuracy when given a small amount of training data.
The degradation of macro-mechanical properties of shield tunnel segments
Authors: Yin Rongrong , Hu Jie , Liu Yu , Wu Qing , Zhang Chenchen , Wang Yuxin
Published: December 2018

In this paper, the degradation of mechanical properties for eccentrically compressed members was investigated by testing the bearing capacities under the combined effect of load, water permeation and salt environment of chloride and sulfate. The results showed that: (1) the bearing capacity of eccentric compression members under “Seepage stress field” increased with the increase of time; (2) when suffering the combined action of chloride and sulfate, the bearing capacity of eccentric compression members under “Seepage stress field” increased in the early stage of corrosion. However, the bearing capacity decreased afterwards. The higher the ions concentration, the greater the descent; (3) the greater the eccentricity, the greater the vertical displacement of eccentric compression members and the smaller the ultimate bearing capacity.
Some New Dissipative Chaotic Systems with Cyclic Symmetry
Authors: Rajagopal Karthikeyan , Panahi Shirin , Karthikeyan Anitha , Alsaedi Ahmed , Pham Viet-Thanh , Hayat Tasawar
Published: December 2018

Designing new chaotic system with specific features is an interesting field in nonlinear dynamics. In this paper, some new chaotic systems with cyclic symmetry are proposed. In order to understand the overall behavior of such systems, the dynamical analyses such as stability analysis, bifurcation and Lyapunov exponent analysis are done. The accurate examination of bifurcation plot represents that these systems are multistable which makes them more interesting. Also, the basin of attraction of these systems is investigated to detect the type of attractors of these systems which are self-excited. Finally, the circuit implementation is carried out to show their feasibility.
Hopf Cyclicity and Global Dynamics for a Predator–Prey System of Leslie Type with Simplified Holling Type IV Functional Response
Authors: Dai Yanfei , Zhao Yulin
Published: December 2018

This paper is concerned with a predator–prey model of Leslie type with simplified Holling type IV functional response, provided that it has either a unique nondegenerate positive equilibrium or three distinct positive equilibria. The type and stability of each equilibrium, Hopf cyclicity of each weak focus, and the number and distribution of limit cycles in the first quadrant are studied. It is shown that every equilibrium is not a center. If the system has a unique positive equilibrium which is a weak focus, then its order is at most [Formula: see text] and it has Hopf cyclicity [Formula: see text]. Moreover, some explicit conditions for the global stability of the unique equilibrium are established by applying Dulac’s criterion and constructing the Lyapunov function. If the system has three distinct positive equilibria, then one of them is a saddle and the others are both anti-saddles. For two anti-saddles, we prove that the Hopf cyclicity for the anti-saddle with smaller abscissa (resp., bigger abscissa) is [Formula: see text] (resp., [Formula: see text]). Furthermore, if both anti-saddle positive equilibria are weak foci, then they are unstable weak foci of order one. Moreover, one limit cycle can bifurcate from each of them simultaneously. Numerical simulations show that there is also a big stable limit cycle enclosing these two small limit cycles.
Hidden Extreme Multistability, Antimonotonicity and Offset Boosting Control in a Novel Fractional-Order Hyperchaotic System Without Equilibrium
Authors: Zhang Sen , Zeng Yicheng , Li Zhijun , Zhou Chengyi
Published: December 2018

Recently, the notion of hidden extreme multistability and hidden attractors is very attractive in chaos theory and nonlinear dynamics. In this paper, by utilizing a simple state feedback control technique, a novel 4D fractional-order hyperchaotic system is introduced. Of particular interest is that this new system has no equilibrium, which indicates that its attractors are all hidden and thus Shil’nikov method cannot be applied to prove the existence of chaos for lacking hetero-clinic or homo-clinic orbits. Compared with other fractional-order chaotic or hyperchaotic systems, this new system possesses three unique and remarkable features: (i) The amazing and interesting phenomenon of the coexistence of infinitely many hidden attractors with respect to same system parameters and different initial conditions is observed, meaning that hidden extreme multistability arises. (ii) By varying the initial conditions and selecting appropriate system parameters, the striking phenomenon of antimonotonicity is first discovered, especially in such a fractional-order hyperchaotic system without equilibrium. (iii) An attractive special feature of the convenience of offset boosting control of the system is also revealed. The complex and rich hidden dynamic behaviors of this system are investigated by using conventional nonlinear analysis tools, including equilibrium stability, phase portraits, bifurcation diagram, Lyapunov exponents, spectral entropy complexity, and so on. Furthermore, a hardware electronic circuit is designed and implemented. The hardware experimental results and the numerical simulations of the same system on the Matlab platform are well consistent with each other, which demonstrates the feasibility of this new fractional-order hyperchaotic system.
Non-singular solutions of GradEla models for dislocations: An extension to fractional GradEla
Authors: Parisis K. , Konstantopoulos I. , Aifantis E. C.
Published: December 2018

An account of non-singular solutions of gradient elasticity (GradEla) models for dislocations, along with clarifications of certain issues raised on previously published results, is given. Then, an extension to fractional GradEla solutions is pursued and certain preliminary results on this emerging topic are listed.
Carnian (Late Triassic) C-isotope excursions, environmental changes, and biotic turnover: a global perturbation of the Earth's surface system
Authors: Dal Corso Jacopo , Ruffell Alastair , Preto Nereo
Published: December 2018

Here we present the second part of the special thematic issue on the Carnian Pluvial Episode (CPE). In this issue, two works on terrestrial sedimentological and floral changes linked to the CPE, and new carbon isotope records from Oman and China are presented. The papers published in this issue complement those contained in volume 175 issue 6; they altogether give an almost complete vision of the state-of-the-art about the CPE, including the many conundrums.
Paris Koutris Speaks Out on a Theoretical Model for Query Processing
Authors: Winslett Marianne , Braganholo Vanessa
Published: December 2018

Welcome to the ACM SIGMOD Record's series of interviews with distinguished members of the database community. I'm Marianne Winslett, and today we're at SIGMOD 2017 in Chicago. I have with me Paris Koutris, who won the 2016 ACM SIGMOD Jim Gray Dissertation Award for his thesis entitled "Query Processing in Massively Parallel Systems." Paris is now a professor at the University of Wisconsin-Madison, and he did his Ph.D. work with Dan Suciu at the University of Washington.
The New and Improved SQL
Authors: Michels Jan , Hare Keith , Kulkarni Krishna , Zuzarte Calisto , Liu Zhen Hua , Hammerschmidt Beda , Zemke Fred
Published: December 2018

SQL:2016 (officially called ISO/IEC 9075:2016, Information technology - Database languages - SQL) was published in December of 2016, replacing SQL:2011 as the most recent revision of the SQL standard. This paper gives an overview of the most important new features in SQL:2016.
The Complex Event Recognition Group
Authors: Alevizos Elias , Artikis Alexander , Katzouris Nikos , Michelioudakis Evangelos , Paliouras Georgios , Paliouras Georgios
Published: December 2018

The Complex Event Recognition (CER) group is a research team, affiliated with the National Centre of Scientific Research "Demokritos" in Greece. The CER group works towards advanced and efficient methods for the recognition of complex events in a multitude of large, heterogeneous and interdependent data streams. Its research covers multiple aspects of complex event recognition, from efficient detection of patterns on event streams to handling uncertainty and noise in streams, and machine learning techniques for inferring interesting patterns. Lately, it has expanded to methods for forecasting the occurrence of events. It was founded in 2009 and currently hosts eight senior and junior researchers, working regularly with under-graduate students.
DANTE
Authors: Bhowmick Sourav S. , Xiaokui Xiao Xiaokui
Published: December 2018

The data management group at the Nanyang Technological University (dante) was founded in 2009 by the first author when the School of Computer Science and Engineering hired two young faculty members in this area. The group currently consists of three faculty members and more than twenty graduate students, research assistants, and postdocs. Our alumni include faculty members at the Chinese University of Hong Kong, National University of Singapore, University of New South Wales, and several researchers and engineers at Facebook, Google, eBay, Huawei, and other technology companies. The group's major funding is from the Ministry of Education in Singapore, National Research Foundation, and companies such as Huawei.
Progress Indication for Machine Learning Model Building
Authors: Luo Gang
Published: December 2018

Progress indicators are desirable for machine learning model building that often takes a long time, by continuously estimating the remaining model building time and the portion of model building work that has been finished. Recently, we proposed a high-level framework using system approaches to support nontrivial progress indicators for machine learning model building, but offered no detailed implementation technique. It remains to be seen whether it is feasible to provide such progress indicators. In this paper, we fill this gap and give the first demonstration that offering such progress indicators is viable. We describe detailed progress indicator implementation techniques for three major, supervised machine learning algorithms. We report an implementation of these techniques in Weka.
Research Issues of Outlier Detection in Trajectory Streams Using GPUs
Authors: Leal Eleazar , Gruenwald Le
Published: December 2018

The widespread availability of sensors like GPS and traffic cameras has made it possible to collect large amounts of spatio-temporal data. One such type of data are trajectories, each of which consists of a time-ordered sequence of positions that a moving object occupies in space as time goes by. Trajectories can be streamed in real time from sensors, and because of this, they capture the current state of moving objects. For this reason, trajectories can be used in applications such as the real-time detection of senior citizens who have just fallen or who have just gotten lost outdoors, the real-time detection of drunk drivers, and the real-time detection of enemy forces in the battlefield. These applications involve the identification of trajectories with anomalous behaviors, and require fast processing in order to take immediate preventive action. However, outlier detection poses challenges stemming from both the complexity of the data and of the task. One way to address this is through parallel architectures like GPUs. In this paper, we present the problem of outlier detection in trajectory streams, and discuss the research issues that should be addressed by new outlier detection techniques for trajectory streams on GPUs.
SOFSAT
Authors: Karmaker Santu Shubhra Kanti , Geigle Chase , Ferguson Duncan , Cope William , Kalantzis Mary , Searsmith Duane , Zhai Chengxiang
Published: December 2018

As data reported by humans about our world, text data play a very important role in all data mining applications, yet how to develop a general text analysis system to sup- port all text mining applications is a difficult challenge. In this position paper, we introduce SOFSAT, a new frame- work that can support set-like operators for semantic analy- sis of natural text data with variable text representations. It includes three basic set-like operators|TextIntersect, Tex- tUnion, and TextDi erence|that are analogous to the cor- responding set operators intersection, union, and di erence, respectively, which can be applied to any representation of text data, and di erent representations can be combined via transformation functions that map text to and from any rep- resentation. Just as the set operators can be exibly com- bined iteratively to construct arbitrary subsets or supersets based on some given sets, we show that the correspond- ing text analysis operators can also be combined exibly to support a wide range of analysis tasks that may require di erent work ows, thus enabling an application developer to \program" a text mining application by using SOFSAT as an application programming language for text analysis. We discuss instantiations and implementation strategies of the framework with some speci c examples, present ideas about how the framework can be implemented by exploit- ing/extending existing techniques, and provide a roadmap for future research in this new direction.
Informing the uninformed: a multitier approach to uncover students’ misconceptions on cardiovascular physiology
Authors: Versteeg Marjolein , Wijnen-Meijer Marjo , Steendijk Paul
Published: December 2018

Misconceptions about physiology are a major threat to accurate scientific and clinical reasoning in medical education. Awareness is often mentioned as a prerequisite to achieve conceptual understanding; however, students are frequently unaware of their incorrect understanding. We explored the multitier approach as a tool to obtain insight into students’ awareness and misconceptions regarding cardiovascular physiology. Biomedical sciences students ( N = 81) participated in a diagnostic multitier assessment on cardiovascular physiology. Each question consisted of an answer tier and an explanation tier. Both tiers were paired with confidence tiers, i.e., 5-point Likert scales, which were used as an indicator for metacognitive evaluation, i.e., awareness. The average test score was 3.07 (maximum 4.0) for the answer tier only, and reduced to 1.57 when answer and explanation tiers were combined. A weak correlation ( R2= 0.13, P = 0.001) between students’ confidence and their test scores was found for the combined responses. Correct combined answers were associated with an increase in confidence score of 0.27 vs. incorrect answers. Using a Bland-Altman analysis, we showed that students generally overestimated their knowledge. In total, 28.7% of all responses were classified as misconceptions, defined as incorrect answers paired with high confidence. In all, findings indicate that the multitier approach is useful to study students’ conceptual understanding and uncover misconceptions on cardiovascular physiology. Furthermore, this study supports the need for metacognitive measures in order to improve teaching and learning in medical education.
Muscle metaboreflex activation via postexercise ischemia as a tool for teaching cardiovascular physiology for undergraduate students
Authors: Teixeira André L. , Samora Milena , Vianna Lauro C.
Published: December 2018

The cardiovascular responses to exercise are mediated by several interactive neural mechanisms, including central command, arterial baroreflex, and skeletal muscle mechano- and metaboreflex. In humans, muscle metaboreflex activation can be isolated via postexercise ischemia (PEI), which increases sympathetic nerve activity and partially maintains the exercise-induced increase in arterial blood pressure. Here, we describe a practical laboratory class using PEI as a simple and useful technique to teach cardiovascular physiology. In an undergraduate exercise physiology class ( n = 47), a traditional 4-h lecture was conducted discussing the neural control mechanisms of cardiovascular regulation during exercise. Thereafter, eight students (4 men and 4 women) were selected to participate as a volunteer of a practical laboratory class. Each participant performed 90 s of isometric handgrip exercise at 40% of maximal voluntary contraction, followed by 3 min of PEI. Arterial blood pressure and heart rate were measured by digital monitors at rest and during isometric handgrip, PEI, and recovery. In addition, blood samples were collected from the tip of the exercising finger for blood lactate analyses. After the laboratory class, a survey was given to determine the perceptions of the students. The findings demonstrate that this laboratory class has proved to be highly popular with students, who self-reported a significant improvement in their understanding of several aspects of cardiovascular regulation during exercise.
Motion sickness as metaphor: engaging with diversity in STEM
Authors: Bergstrom Rachel A.
Published: December 2018

Science, technology, engineering, and math (STEM) continue to work to increase the diversity of the fields, yet there are still significant historical and societal hurdles to be overcome before we reach full representation throughout STEM. The concept of science identity has become a point of interest in this process; it has been suggested that development of one’s identity as a scientist is critical to persistence in the field. Metaphors that are rooted in bodily experience can provide a starting point to understand abstract concepts, including science identity and how we as STEM educators respond to increasing diversity within our fields. Given the history of STEM being predominantly populated by people who are white and male, disorientation or discomfort with increasing diversity is not unexpected, and many women and people of color report discrimination and marginalization as a part of their experience in STEM. Here I present a neuroscience-based metaphor that can serve as a starting point for understanding some of the potential disorientation or discomfort that we may experience as we engage with the increasing diversity of STEM and acknowledge this experience as a normal but temporary part of the process of growth and development as a field. I encourage the development and use of further discipline-based metaphors to enhance our discussion and understanding of this important work.
GEP100/ARF6 regulates VEGFR2 signaling to facilitate high-glucose-induced epithelial-mesenchymal transition and cell permeability in retinal pigment epithelial cells
Authors: You Zhi-Peng , Chen Shan-Shan , Yang Zhong-Yi , Li Shu-Rong , Xiong Fan , Liu Ting , Fu Shu-Hua
Published: December 2018

Cell permeability and epithelial-mesenchymal transition (EMT) were found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism. ARPE-19 cell line or primary retinal pigment epithelial (RPE) cells were cultured under high or normal glucose conditions. Specific shRNAs were employed to knock down ADP-ribosylation factor 6 (ARF6), GEP100, or VEGF receptor 2 (VEGFR2) in ARPE-19 or primary RPE cells. Cell migration ability was measured using Transwell assay. Western blotting was used to measure indicated protein levels. RPE cells treated with high glucose showed increased cell migration, paracellular permeability, EMT, and expression of VEGF. Knockdown of VEGFR2 inhibited the high-glucose-induced effects on RPE cells via inactivation of ARF6 and MAPK pathways. Knockdown ARF6 or GEP100 led to inhibition of high-glucose-induced effects via inactivation of VEGFR2 pathway. Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2. High-glucose enhances EMT and cell permeability of RPE cells through activation of VEGFR2 and ARF6/GEP100 pathways, which form a positive feedback loop to maximize the activation of VEGF/VEGFR2 signaling.
Histamine causes influx via T-type voltage-gated calcium channels in an enterochromaffin tumor cell line: potential therapeutic target in adverse food reactions
Authors: Pfanzagl Beatrix , Zevallos Victor F. , Schuppan Detlef , Pfragner Roswitha , Jensen-Jarolim Erika
Published: December 2018

The P-STS human ileal neuroendocrine tumor cells, as a model for gut enterochromaffin cells, are strongly and synergistically activated by histamine plus acetylcholine (ACh), presumably via histamine 4 receptors, and weakly activated by histamine alone. Sensing these signals, enterochromaffin cells could participate in intestinal intolerance or allergic reactions to food constituents associated with elevated histamine levels. In this study we aimed to analyze the underlying molecular mechanisms. Inhibition by mepyramine and mibefradil indicated that histamine alone caused a rise in intracellular calcium concentration ([Ca2+]i) via histamine 1 receptors involving T-type voltage-gated calcium channels (VGCCs). Sensitivity to histamine was enhanced by pretreatment with the inflammatory cytokine tumor necrosis factor-α (TNF-α). In accordance with the relief it offers some inflammatory bowel disease patients, otilonium bromide, a gut-impermeable inhibitor of T-type (and L-type) VGCCs and muscarinic ACh receptors, efficiently inhibited the [Ca2+]i responses induced by histamine plus ACh or by histamine alone in P-STS cells. It will take clinical studies to show whether otilonium bromide has promise for the treatment of adverse food reactions. The cells did not react to the nutrient constituents glutamate, capsaicin, cinnamaldehyde, or amylase-trypsin inhibitors and the transient receptor potential channel vanilloid 4 agonist GSK-1016790A. The bacterial product butyrate evoked a rise in [Ca2+]i only when added together with ACh. Lipopolysaccharide had no effect on [Ca2+]i despite the presence of Toll-like receptor 4 protein. Our results indicate that inflammatory conditions with elevated levels of TNF-α might enhance histamine-induced serotonin release from intestinal neuroendocrine cells.

NEW & NOTEWORTHY We show that histamine synergistically enhances the intracellular calcium response to the physiological agonist acetylcholine in human ileal enterochromaffin tumor cells. This synergistic activation and cell activation by histamine alone largely depend on T-type voltage-gated calcium channels and are inhibited by the antispasmodic otilonium bromide. The cells showed no response to wheat amylase-trypsin inhibitors, suggesting that enterochromaffin cells are not directly involved in nongluten wheat sensitivity.
“I don’t get no respect”: the role of chloride in acute kidney injury
Authors: Rein Joshua L. , Coca Steven G.
Published: December 2018

Acute kidney injury (AKI) is a major public health problem that complicates 10–40% of hospital admissions. Importantly, AKI is independently associated with increased risk of progression to chronic kidney disease, end-stage renal disease, cardiovascular events, and increased risk of in-hospital and long-term mortality. The chloride content of intravenous fluid has garnered much attention over the last decade, as well as its association with excess use and adverse outcomes, including AKI. Numerous studies show that changes in serum chloride concentration, independent of serum sodium and bicarbonate, are associated with increased risk of AKI, morbidity, and mortality. This comprehensive review details the complex renal physiology regarding the role of chloride in regulating renal blood flow, glomerular filtration rate, tubuloglomerular feedback, and tubular injury, as well as the findings of clinical research related to the chloride content of intravenous fluids, changes in serum chloride concentration, and AKI. Chloride is underappreciated in both physiology and pathophysiology. Although the exact mechanism is debated, avoidance of excessive chloride administration is a reasonable treatment option for all patients and especially in those at risk for AKI. Therefore, high-risk patients and those with “incipient” AKI should receive balanced solutions rather than normal saline to minimize the risk of AKI.
Impact of obesity as an independent risk factor for the development of renal injury: implications from rat models of obesity
Authors: McPherson Kasi C. , Shields Corbin A. , Poudel Bibek , Fizer Brianca , Pennington Alyssa , Szabo-Johnson Ashley , Thompson Willie L. , Cornelius Denise C. , Williams Jan M.
Published: December 2018

Diabetes and hypertension are the major causes of chronic kidney disease (CKD). Epidemiological studies within the last few decades have revealed that obesity-associated renal disease is an emerging epidemic and that the increasing prevalence of obesity parallels the increased rate of CKD. This has led to the inclusion of obesity as an independent risk factor for CKD. A major complication when studying the relationship between obesity and renal injury is that cardiovascular and metabolic disorders that may result from obesity including hyperglycemia, hypertension, and dyslipidemia, or the cluster of these disorders [defined as the metabolic syndrome, (MetS)] also contribute to the development and progression of renal disease. The associations between hyperglycemia and hypertension with renal disease have been reported extensively in patients suffering from obesity. Currently, there are several obese rodent models (high-fat diet-induced obesity and leptin signaling dysfunction) that exhibit characteristics of MetS. However, the available obese rodent models currently have not been used to investigate the impact of obesity alone on the development of renal injury before hypertension and/or hyperglycemia. Therefore, the aim of this review is to describe the incidence and severity of renal disease in these rodent models of obesity and determine which models are suitable to study the independent effects obesity on the development and progression of renal disease.
Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial cells injury by regulating mitochondrial dysfunction and NLRP3 inflammasome activation
Authors: Xu Yao , Wang Jingjing , Xu Wangjie , Ding Feng , Ding Wei
Published: December 2018

Accumulating evidence demonstrates that mitochondrial dysfunction and inflammasome activation play a critical role in the pathogenesis of renal tubular injury through the production of reactive oxygen species and cytokines. Prohibitin 2 (PHB2) is a newly identified intracellular receptor of mitophagy (a type of autophagy) that mediates selective removal of damaged mitochondria, and it could possibly play a renoprotective role in kidney disease. In this study, we confirmed that autophagy is activated in tubular epithelial cells treated with angiotensin II and that inhibition of autophagy results in tubular cell injury. Strikingly, PHB2 knockdown reduced the level of mitophagy and augmented cell death, while overexpression of PHB2 provided protection against pyrin domain-containing protein 3 (NLRP3)-induced inflammatory pathways through amelioration of mitochondrial dysfunction. Our research is the first to experimentally demonstrate the role of PHB2 in renal proximal tubular cells and thereby to provide a better understanding of how autophagy modulates inflammation in renal tubules. These data highlight PHB2 as a therapeutic target in the future treatment of CKD.
Slowed sensory reweighting and postural illusions in older adults: the moving platform illusion
Authors: Craig Chesney E. , Doumas Michail
Published: December 2018

We investigated whether postural aftereffects witnessed during transitions from a moving to a stable support are accompanied by a delayed perception of platform stabilization in older adults, in two experiments. In experiment 1, postural sway and muscle cocontraction were assessed in 11 healthy young, 11 healthy older, and 11 fall-prone older adults during blindfolded stance on a fixed platform, followed by a sway-referenced platform and then by a fixed platform again. The sway-referenced platform was more compliant for young adults, to induce similar levels of postural sway in both age groups. Participants were asked to press a button whenever they perceived that the platform had stopped moving. Both older groups showed significantly larger and longer postural sway aftereffects during platform stabilization compared with young adults, which were pronounced in fall-prone older adults. In both older groups elevated muscle cocontraction aftereffect was also witnessed. Importantly, these aftereffects were accompanied by an illusory perception of prolonged platform movement. After this, experiment 2 examined whether this illusory perception was a robust age effect or an experimental confound due to greater surface compliance in young adults, which could create a larger perceptual discrepancy between moving and stable conditions. Despite exposure to the same surface compliance levels during sway-reference, the perceptual illusion was maintained in experiment 2 in a new group of 14 healthy older adults compared with 11 young adults. In both studies, older adults took five times longer than young adults to perceive platform stabilization. This supports that sensory reweighting is inefficient in older adults.

NEW & NOTEWORTHY This is the first paper to show that postural sway aftereffects witnessed in older adults after platform stabilization may be due to a perceptual illusion of platform movement. Surprisingly, in both experiments presented it took older adults five times longer than young adults to perceive platform stabilization. This supports a hypothesis of less efficient sensory reintegration in this age group, which may delay the formation of an accurate postural percept.
Automated home cage training of mice in a hold-still center-out reach task
Authors: Bollu Tejapratap , Whitehead Samuel C. , Prasad Nikil , Walker Jackson , Shyamkumar Nitin , Subramaniam Raghav , Kardon Brian , Cohen Itai , Goldberg Jesse H.
Published: December 2018

An obstacle to understanding neural mechanisms of movement is the complex, distributed nature of the mammalian motor system. Here we present a novel behavioral paradigm for high-throughput dissection of neural circuits underlying mouse forelimb control. Custom touch-sensing joysticks were used to quantify mouse forelimb trajectories with micron-millisecond spatiotemporal resolution. Joysticks were integrated into computer-controlled, rack-mountable home cages, enabling batches of mice to be trained in parallel. Closed loop behavioral analysis enabled online control of reward delivery for automated training. We used this system to show that mice can learn, with no human handling, a direction-specific hold-still center-out reach task in which a mouse first held its right forepaw still before reaching out to learned spatial targets. Stabilogram diffusion analysis of submillimeter-scale micromovements produced during the hold demonstrate that an active control process, akin to upright balance, was implemented to maintain forepaw stability. Trajectory decomposition methods, previously used in primates, were used to segment hundreds of thousands of forelimb trajectories into millions of constituent kinematic primitives. This system enables rapid dissection of neural circuits for controlling motion primitives from which forelimb sequences are built.

NEW & NOTEWORTHY A novel joystick design resolves mouse forelimb kinematics with micron-millisecond precision. Home cage training is used to train mice in a hold-still center-out reach task. Analytical methods, previously used in primates, are used to decompose mouse forelimb trajectories into kinematic primitives.
Scaling of Motor Output, From Mouse to Humans
Authors: Manuel Marin , Chardon Matthieu , Tysseling Vicki , Heckman C. J.
Published: December 2018

Appropriate scaling of motor output from mouse to humans is essential. The motoneurons that generate all motor output are, however, very different in rodents compared with humans, being smaller and much more excitable. In contrast, feline motoneurons are more similar to those in humans. These scaling differences need to be taken into account for the use of rodents for translational studies of motor output.
Regulation of Ribosome Biogenesis in Skeletal Muscle Hypertrophy
Authors: Figueiredo Vandré Casagrande , McCarthy John J.
Published: December 2018

The ribosome is the enzymatic macromolecular machine responsible for protein synthesis. The rates of protein synthesis are primarily dependent on translational efficiency and capacity. Ribosome biogenesis has emerged as an important regulator of skeletal muscle growth and maintenance by altering the translational capacity of the cell. Here, we provide evidence to support a central role for ribosome biogenesis in skeletal muscle growth during postnatal development and in response to resistance exercise training. Furthermore, we discuss the cellular signaling pathways regulating ribosome biogenesis, discuss how myonuclear accretion affects translational capacity, and explore future areas of investigation within the field.
Evolving and Expanding the Roles of Mitophagy as a Homeostatic and Pathogenic Process
Authors: Gustafsson Åsa B. , Dorn Gerald W.
Published: December 2018

The central functions fulfilled by mitochondria as both energy generators essential for tissue homeostasis and gateways to programmed apoptotic and necrotic cell death mandate tight control over the quality and quantity of these ubiquitous endosymbiotic organelles. Mitophagy, the targeted engulfment and destruction of mitochondria by the cellular autophagy apparatus, has conventionally been considered as the mechanism primarily responsible for mitochondrial quality control. However, our understanding of how, why, and under what specific conditions mitophagy is activated has grown tremendously over the past decade. Evidence is accumulating that nonmitophagic mitochondrial quality control mechanisms are more important to maintaining normal tissue homeostasis whereas mitophagy is an acute tissue stress response. Moreover, previously unrecognized mitophagic regulation of mitochondrial quantity control, metabolic reprogramming, and cell differentiation suggests that the mechanisms linking genetic or acquired defects in mitophagy to neurodegenerative and cardiovascular diseases or cancer are more complex than simple failure of normal mitochondrial quality control. Here, we provide a comprehensive overview of mitophagy in cellular homeostasis and disease and examine the most revolutionary concepts in these areas. In this context, we discuss evidence that atypical mitophagy and nonmitophagic pathways play central roles in mitochondrial quality control, functioning that was previously considered to be the primary domain of mitophagy.