bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetramer Enrichment Reveals the Presence of Phenotypically Diverse Hepatitis C Virus-Specific CD8
+
T Cells in Chronic Infection
Authors: Nitschke Katja , Flecken Tobias , Schmidt Julia , Gostick Emma , Marget Matthias , Neumann-Haefelin Christoph , Blum Hubert E. , Price David A. , Thimme Robert
Published: October 2014

Virus-specific CD8
+
T cells are rarely detectable
ex vivo
by conventional methods during chronic hepatitis C virus (HCV) infection. In this study, however, we were able to detect and characterize HCV-specific CD8
+
T cells in all chronically HCV genotype 1a-infected, HLA-A*02:01-positive patients analyzed by performing major histocompatibility complex (MHC) class I tetramer enrichment. Two-thirds of these enriched HCV-specific CD8
+
T-cell populations displayed an effector memory phenotype, whereas, surprisingly, one-third displayed a naive-like phenotype despite ongoing viral replication. CD8
+
T cells with an effector memory phenotype could not expand
in vitro
, suggesting exhaustion of these cells. Interestingly, some of the naive-like CD8
+
T cells proliferated vigorously upon
in vitro
priming, whereas others did not. These differences were linked to the corresponding viral sequences in the respective patients. Indeed, naive-like CD8
+
T cells from patients with the consensus sequence in the corresponding T-cell epitope did not expand
in vitro
. In contrast, in patients displaying sequence variations, we were able to induce HCV-specific CD8
+
T-cell proliferation, which may indicate infection with a variant virus. Collectively, these data reveal the presence of phenotypically and functionally diverse HCV-specific CD8
+
T cells at very low frequencies that are detectable in all chronically infected patients despite viral persistence.

IMPORTANCE
In this study, we analyzed CD8
+
T-cell responses specific for HLA-A*02:01-restricted epitopes in chronically HCV-infected patients, using MHC class I tetramer enrichment. Importantly, we could detect HCV-specific CD8
+
T-cell populations in all patients. To further characterize these HCV-specific CD8
+
T-cell populations that are not detectable using conventional techniques, we performed phenotypic, functional, and viral sequence analyses. These data revealed different mechanisms for CD8
+
T-cell failure in HCV infection, including T-cell exhaustion, viral escape, and functional impairment of naive-like HCV-specific CD8
+
T cells.
Contact-Induced Mitochondrial Polarization Supports HIV-1 Virological Synapse Formation
Authors: Groppelli Elisabetta , Starling Shimona , Jolly Clare
Published: October 2014

Rapid HIV-1 spread between CD4 T lymphocytes occurs at retrovirus-induced immune cell contacts called virological synapses (VS). VS are associated with striking T cell polarization and localized virus budding at the site of contact that facilitates cell-cell spread. In addition to this, spatial clustering of organelles, including mitochondria, to the contact zone has been previously shown. However, whether cell-cell contact specifically induces dynamic T cell remodeling during VS formation and what regulates this process remain unclear. Here, we report that contact between an HIV-1-infected T cell and an uninfected target T cell specifically triggers polarization of mitochondria concomitant with recruitment of the major HIV-1 structural protein Gag to the site of cell-cell contact. Using fixed and live-cell imaging, we show that mitochondrial and Gag polarization in HIV-1-infected T cells occurs within minutes of contact with target T cells, requires the formation of stable cell-cell contacts, and is an active, calcium-dependent process. We also find that perturbation of mitochondrial polarization impairs cell-cell spread of HIV-1 at the VS. Taken together, these data suggest that HIV-1-infected T cells are able to sense and respond to contact with susceptible target cells and undergo dynamic cytoplasmic remodeling to create a synaptic environment that supports efficient HIV-1 VS formation between CD4 T lymphocytes.

IMPORTANCEHIV-1 remains one of the major global health challenges of modern times. The capacity of HIV-1 to cause disease depends on the virus's ability to spread between immune cells, most notably CD4 T lymphocytes. Cell-cell transmission is the most efficient way of HIV-1 spread and occurs at the virological synapse (VS). The VS forms at the site of contact between an infected cell and an uninfected cell and is characterized by polarized assembly and budding of virions and clustering of cellular organelles, including mitochondria. Here, we show that cell-cell contact induces rapid recruitment of mitochondria to the contact site and that this supports efficient VS formation and consequently cell-cell spread. Additionally, we observed that cell-cell contact induces a mitochondrion-dependent increase in intracellular calcium, indicative of cellular signaling. Taken together, our data suggest that VS formation is a regulated process and thus a potential target to block HIV-1 cell-cell spread.
Murine Cytomegalovirus Is Not Restricted to the House Mouse Mus musculus domesticus: Prevalence and Genetic Diversity in the European House Mouse Hybrid Zone
Authors: Goüy de Bellocq Joëlle , Baird Stuart J. E. , Albrechtová Jana , Sobeková Karolína , Piálek Jaroslav
Published: October 2014

Murine cytomegalovirus (MCMV) is a betaherpesvirus of the house mouse,
Mus musculus domesticus
. It is a common infectious agent of wild mice and a highly studied pathogen of the laboratory mouse. Betaherpesviruses are specific to their hosts, and it is not known if other
Mus
taxa carry MCMV or if it is restricted to
M. m. domesticus
. We sampled mice over a 145-km transect of Bavaria-Bohemia crossing a hybrid zone between
M. m. domesticus
and
Mus musculus musculus
in order to investigate the occurrence of MCMV in two
Mus
subspecies and to test the limits of the specificity of the virus for its host. We hypothesized that if the two subspecies carry MCMV and if the virus is highly specific to its host, divergent MCMV lineages would have codiverged with their hosts and would have a geographical distribution constrained by the host genetic background. A total of 520 mice were tested by enzyme-linked immunosorbent assay (ELISA) and/or nested PCR targeting the M94 gene. Seropositive and PCR-positive individuals were found in both
Mus
subspecies. Seroprevalence was high, at 79.4%, but viral DNA was detected in only 41.7% of mice. Sequencing revealed 20 haplotypes clustering in 3 clades that match the host genetic structure in the hybrid zone, showing 1 and 2 MCMV lineages in
M. m. domesticus
and
M. m. musculus
, respectively. The estimated time to the most recent common ancestor (1.1 million years ago [Mya]) of the MCMVs matches that of their hosts. In conclusion, MCMV has coevolved with these hosts, suggesting that its diversity in nature may be underappreciated, since other members of the subgenus
Mus
likely carry different MCMVs.

IMPORTANCE
Murine cytomegalovirus (MCMV) is a betaherpesvirus of the house mouse,
Mus musculus domesticus
, an important lab model for human cytomegalovirus (HCMV) infection. The majority of lab studies are based on only two strains of MCMVs isolated from
M. m. domesticus
, Smith and K181, the latter derived from repeated passage of Smith in mouse submaxillary glands. The presence of MCMV in other members of the
Mus
subgenus had not even been investigated. By screening mouse samples collected in the European house mouse hybrid zone between
M. m. domesticus
and
M. m. musculus
, we show that MCMV is not restricted to the
M. m. domesticus
subspecies and that MCMVs likely codiverged with their
Mus
hosts. Thus, the diversity of MCMV in nature may be seriously underappreciated, since other members of the subgenus
Mus
likely carry their own MCMV lineages.
Selective Acquisition of Host-Derived ICAM-1 by HIV-1 Is a Matrix-Dependent Process
Authors: Jalaguier Pascal , Cantin Réjean , Maaroufi Halim , Tremblay Michel J.
Published: October 2014

HIV-1 acquires an impressive number of foreign components during its formation. Despite all previous efforts spent studying the nature and functionality of virus-anchored host molecules, the exact mechanism(s) through which such constituents are acquired by HIV-1 is still unknown. However, in the case of ICAM-1, one of the most extensively studied transmembrane proteins found associated with mature virions, the Pr55
Gag
precursor polyprotein appears to be a potential interaction partner. We investigated and characterized at the molecular level the process of ICAM-1 incorporation using initially a Pr55
Gag
-based virus-like particle (VLP) model. Substitution of various domains of Pr55
Gag
, such as the nucleocapsid, SP2, or p6, had no effect on the acquisition of ICAM-1. We found that the structural matrix protein (MA) is mandatory for ICAM-1 incorporation within VLPs, and we confirmed this novel observation with the replication-competent HIV-1 molecular clone NL4.3. Additional studies suggest that the C-terminal two-thirds of MA, and especially 13 amino acids positioned inside the fifth α-helix, are important. Moreover, based on three-dimensional (3D) modeling of protein-protein interactions (i.e., protein-protein docking) and further validation by a virus capture assay, we found that a series of acidic residues in the MA domain interact with basic amino acids located in the ICAM-1 cytoplasmic tail. Our findings provide new insight into the molecular mechanism governing the acquisition of ICAM-1, a host molecule known to enhance HIV-1 infectivity in a significant manner. Altogether, these observations offer a new avenue for the development of antiviral therapeutics that are directed at a target of host origin.

IMPORTANCE
Intercellular adhesion molecule 1 (ICAM-1) is a cell surface host component known to be efficiently inserted within emerging HIV-1 particles. It has been demonstrated that host-derived ICAM-1 molecules act as a strong attachment factor and increase HIV-1 infectivity substantially. Despite previous efforts spent studying virus-associated host molecules, the precise mechanism(s) through which such constituents are inserted within emerging HIV-1 particles still remains obscure. Previous data suggest that the Pr55
Gag
precursor polyprotein appears as a potential interaction partner with ICAM-1. In the present study, we demonstrate that the HIV-1 matrix domain plays a key role in the ICAM-1 incorporation process. Some observations were confirmed with whole-virus preparations amplified in primary human cells, thereby providing physiological significance to our data.
Entry Mechanisms of Herpes Simplex Virus 1 into Murine Epidermis: Involvement of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors
Authors: Petermann Philipp , Thier Katharina , Rahn Elena , Rixon Frazer J. , Bloch Wilhelm , Özcelik Semra , Krummenacher Claude , Barron Martin J. , Dixon Michael J. , Scheu Stefanie , Pfeffer Klaus , Knebel-Mörsdorf Dagmar
Published: October 2014

Skin keratinocytes represent a primary entry site for herpes simplex virus 1 (HSV-1)
in vivo
. The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) act as efficient receptors for both serotypes of HSV and are sufficient for disease development mediated by HSV-2 in mice. How HSV-1 enters skin and whether both nectin-1 and HVEM are involved are not known. We addressed the impact of nectin-1 during entry of HSV-1 into murine epidermis and investigated the putative contribution of HVEM. Using
ex vivo
infection of murine epidermis, we showed that HSV-1 entered the basal keratinocytes of the epidermis very efficiently. In nectin-1-deficient epidermis, entry was strongly reduced. Almost no entry was observed, however, in nectin-1-deficient keratinocytes grown in culture. This observation correlated with the presence of HVEM on the keratinocyte surface in epidermis and with the lack of HVEM expression in nectin-1-deficient primary keratinocytes. Our results suggest that nectin-1 is the primary receptor in epidermis, while HVEM has a more limited role. For primary murine keratinocytes, on which nectin-1 acts as a single receptor, electron microscopy suggested that HSV-1 can enter both by direct fusion with the plasma membrane and via endocytic vesicles. Thus, we concluded that nectin-1 directs internalization into keratinocytes via alternative pathways. In summary, HSV-1 entry into epidermis was shown to strongly depend on the presence of nectin-1, but the restricted presence of HVEM can potentially replace nectin-1 as a receptor, illustrating the flexibility employed by HSV-1 to efficiently invade tissue
in vivo
.

IMPORTANCE
Herpes simplex virus (HSV) can cause a range of diseases in humans, from uncomplicated mucocutaneous lesions to life-threatening infections. The skin is one target tissue of HSV, and the question of how the virus overcomes the protective skin barrier and penetrates into the tissue to reach its receptors is still open. Previous studies analyzing entry into cells grown
in vitro
revealed nectin-1 and HVEM as HSV receptors. To explore the contributions of nectin-1 and HVEM to entry into a natural target tissue, we established an
ex vivo
infection model. Using nectin-1- or HVEM-deficient mice, we demonstrated the distinct involvement of nectin-1 and HVEM for HSV-1 entry into epidermis and characterized the internalization pathways. Such advances in understanding the involvement of receptors in tissue are essential preconditions for unraveling HSV invasion of skin, which in turn will allow the development of antiviral reagents.
Optimization of drug–drug interaction alert rules in a pediatric hospital's electronic health record system using a visual analytics dashboard
Authors: Simpao Allan F , Ahumada Luis M , Desai Bimal R , Bonafide Christopher P , Gálvez Jorge A , Rehman Mohamed A , Jawad Abbas F , Palma Krisha L , Shelov Eric D
Published: October 2014

Objective To develop and evaluate an electronic dashboard of hospital-wide electronic health record medication alerts for an alert fatigue reduction quality improvement project.

Methods We used visual analytics software to develop the dashboard. We collaborated with the hospital-wide Clinical Decision Support committee to perform three interventions successively deactivating clinically irrelevant drug–drug interaction (DDI) alert rules. We analyzed the impact of the interventions on care providers’ and pharmacists’ alert and override rates using an interrupted time series framework with piecewise regression.

Results We evaluated 2 391 880 medication alerts between January 31, 2011 and January 26, 2014. For pharmacists, the median alert rate prior to the first DDI deactivation was 58.74 alerts/100 orders (IQR 54.98–60.48) and 25.11 alerts/100 orders (IQR 23.45–26.57) following the three interventions (p<0.001). For providers, baseline median alert rate prior to the first round of DDI deactivation was 19.73 alerts/100 orders (IQR 18.66–20.24) and 15.11 alerts/100 orders (IQR 14.44–15.49) following the three interventions (p<0.001). In a subgroup analysis, we observed a decrease in pharmacists’ override rates for DDI alerts that were not modified in the system from a median of 93.06 overrides/100 alerts (IQR 91.96–94.33) to 85.68 overrides/100 alerts (IQR 84.29–87.15, p<0.001). The medication serious safety event rate decreased during the study period, and there were no serious safety events reported in association with the deactivated alert rules.

Conclusions An alert dashboard facilitated safe rapid-cycle reductions in alert burden that were temporally associated with lower pharmacist override rates in a subgroup of DDIs not directly affected by the interventions; meanwhile, the pharmacists’ frequency of selecting the ‘cancel’ option increased. We hypothesize that reducing the alert burden enabled pharmacists to devote more attention to clinically relevant alerts.
Curative reconstruction of a cerebral aneurysm by flow diversion with the Pipeline embolisation device in a patient with Loeys-Dietz syndrome
Authors: Colby Geoffrey P , Lin Li-Mei , Zeiler Steven R , Coon Alexander L
Published: October 2014

Loeys-Dietz syndrome is a recently described connective tissue disorder with a natural history of extreme vessel tortuosity and aggressive arterial aneurysm formation and rupture. This is the case of a 23-year-old woman with a large, dysplastic cavernous aneurysm who had successful endovascular treatment by flow diversion with the Pipeline embolisation device. Ten-month follow-up demonstrated complete aneurysm occlusion and curative reconstruction of the parent vessel without evidence of vessel injury or dissection. Endovascular treatment with flow-diverting devices is a valid treatment option and can be performed safely and effectively in this complex patient population.
Veterinary homeopathy: systematic review of medical conditions studied by randomised placebo‐controlled trials
Authors: Mathie Robert T. , Clausen Jürgen
Published: October 2014

A systematic review of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. Using Cochrane methods, this review aims to assess risk of bias and to quantify the effect size of homeopathic intervention compared with placebo for each eligible peer‐reviewed trial. Judgement in seven assessment domains enabled a trial's risk of bias to be designated as low, unclear or high. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specified domains. A trial was considered to be free of vested interest if it was not funded by a homeopathic pharmacy. The 18 eligible RCTs were disparate in nature, representing four species and 11 different medical conditions. Reliable evidence, free from vested interest, was identified in two trials: homeopathic Coli had a prophylactic effect on porcine diarrhoea (odds ratio 3.89, 95 per cent confidence interval [CI], 1.19 to 12.68, P=0.02); and individualised homeopathic treatment did not have a more beneficial effect on bovine mastitis than placebo intervention (standardised mean difference ‐0.31, 95 per cent CI, ‐0.97 to 0.34, P=0.35). Mixed findings from the only two placebo‐controlled RCTs that had suitably reliable evidence precluded generalisable conclusions about the efficacy of any particular homeopathic medicine or the impact of individualised homeopathic intervention on any given medical condition in animals.
Carnivorous pitcher plant species (Sarracenia purpurea) increases root growth in response to nitrogen addition
Authors: Lenihan William , Schultz Rachel
Published: October 2014

Nitrogen (N) deposition from anthropogenic sources can facilitate the encroachment of plant species with high-N demands into nutrient-poor ecosystems such as sphagnum bogs. Prior research has demonstrated that altered leaf morphology of the carnivorous pitcher plant Sarracenia purpurea L. can serve as a biological indicator of increased bog nitrification. Our objective was to assess the effect of N addition on the root morphology of S. purpurea. To make this assessment, nine S. purpurea plants were grown in microcosms with their roots positioned on transparent acrylic tubes so that root growth could be monitored. Three replicate microcosms received either a high-N treatment (1.0 mg NH4-N·L−1), low-N treatment (0.1 mg NH4-N·L−1), or no additional N. After 7 weeks, we scanned the roots with WinRhizo Pro software, recorded leaf dimensions, and measured the dry mass of the roots and leaves. The high-N treatment had significantly greater root length, surface area, and dry biomass than the controls. In contrast, we found no difference in leaf dimensions or aboveground biomass among treatments. The results of this study support our hypothesis that S. purpurea increases root growth to uptake nutrients from the soil under conditions of increased N deposition.
A tolerant lactic acid bacteria, Lactobacillus paracasei, and its immunoregulatory function
Authors: Kou Xiaohong , Chen Qiong , Ju Xiaoying , Liu Huiping , Chen Wenrong , Xue Zhaohui
Published: October 2014

The aim of the present investigation was to isolate a probiotic strain from 23 samples of yurts cheese and 21 samples of kumiss (collected from scattered households in Xinjiang and Inner Mongolia), and from eN-Lac Capsules, a health-promoting product. The isolates were subjected to biochemical characterization analysis and were tested for tolerance to low pH, sodium salt, bile salt, pepsin, and trypsin. 16S DNA sequence analysis was conducted to identify the strain. The possible dose-dependent role of strain LP2 in immunomodulation was investigated using the ICR mouse model (from the Institute of Cancer Research). Daily, we conducted clinical observations, a carbon clearance test, a spleen lymphocyte proliferation test, and measurements of body mass and lymphoid organ index. Natural killer cell activity and delayed-type hypersensitivity reaction were determined. The results showed that 3 selected strains (LP2, LP4, and LP9) had high tolerance to low pH, sodium chloride, and bile salt and were not significantly different from Lactobacillus paracasei in terms of morphology, colony, and biochemistry characterizations. A further tolerance test showed that LP2 had the highest survival rate (90%) under the conditions of pH 3.0, 0.3% bile salt, 10 mg/mL pepsin, and 10 mg/mL trypsin for 24 h. The sequence heterogeneities within the 16S rDNA genes molecularly elucidated that the LP2 belongs to the L. paracasei family, on the basis of a homology of 99.6%. A significant enhanced footpad swelling reaction and natural killer cell activity in the middle-dose (108 cfu/mL) and the high-dose (109 cfu/mL) groups were observed but without obvious dose dependence (P < 0.05). Lymphocyte proliferation was also increased significantly in a dose-dependent manner (P < 0.01) compared with that of the control group, indicating a positive immunoregulatory effect.
Seasonal reproductive anatomy and sperm storage in pleurocerid gastropods (Cerithioidea: Pleuroceridae)
Authors: Whelan Nathan V. , Strong Ellen E.
Published: October 2014

Life histories, including anatomy and behavior, are a critically understudied component of gastropod biology, especially for imperiled freshwater species of Pleuroceridae. This aspect of their biology provides important insights into understanding how evolution has shaped optimal reproductive success and is critical for informing management and conservation strategies. One particularly understudied facet is seasonal variation in reproductive form and function. For example, some have hypothesized that females store sperm over winter or longer, but no study has explored seasonal variation in accessory reproductive anatomy. We examined the gross anatomy and fine structure of female accessory reproductive structures (pallial oviduct, ovipositor) of four species in two genera (round rocksnail, Leptoxis ampla (Anthony, 1855); smooth hornsnail, Pleurocera prasinata (Conrad, 1834); skirted hornsnail, Pleurocera pyrenella (Conrad, 1834); silty hornsnail, Pleurocera canaliculata (Say, 1821)). Histological analyses show that despite lacking a seminal receptacle, females of these species are capable of storing orientated sperm in their spermatophore bursa. Additionally, we found that they undergo conspicuous seasonal atrophy of the pallial oviduct outside the reproductive season, and there is no evidence that they overwinter sperm. The reallocation of resources primarily to somatic functions outside of the egg-laying season is likely an adaptation that increases survival chances during winter months.
An approach to heavy quarkonium spectra
Authors: Cançelik Y. , Gönül B.
Published: October 2014

An application of the recently introduced method [M. Çapak et al., J. Math. Phys. 52, 102102 (2011)] to the bound-state eigenvalue problem in the elementary quarkonium potential V(r) = -a/r + br + cr2 is described, proved and illustrated for [Formula: see text] and [Formula: see text] systems. The quasi- and conditionally-exactly solvable spin-averaged mass spectra of heavy quarkonia are obtained in compact forms. The comparison of the present predictions with those of other theories in the related literature, together with the available data, has shown the success of the model used in this work and also revealed that the use of different confinings in the perturbed Coulomb potential descriptions has no considerable effect on the mass spectra of such systems.
NΩ interaction from two approaches in lattice QCD
Authors: Etminan Faisal , Firoozabadi Mohammad Mehdi
Published: October 2014

We compare the standard finite volume method by Lüscher with the potential method by HAL QCD collaboration, by calculating the ground state energy of N(nucleon)-Ω(Omega) system in 5 S2 channel. We employ 2+1 flavor full QCD configurations on a (1.9 fm )3×3.8 fm lattice at the lattice spacing a≃0.12 fm , whose ud(s) quark mass corresponds to mπ = 875(1) (mK = 916(1)) MeV . We have found that both methods give reasonably consistent results that there is one NΩ bound state at this parameter.
Transport optimization considering the node aggregation ability
Authors: Liu Gang , Li Lian , Guo Jiawei , Li Zheng
Published: October 2014

Using the theories of complex networks and gravitational field, we study the dynamic routing process under the framework of node gravitational field, define the equation of gravitation of travel path to data package and introduce two parameters α and γ for adjusting the dependences of transmission data on the unblocked degree of node, the transmission capacity of node and the path length. Based on the path's attraction, a gravitational field routing strategy under node connection ability constraint is proposed with considering the affect of node aggregation ability to transport process, and a parameter is used to adjust the control strength of routing process to node aggregation ability. In order to clarify the efficiency of suggested method, we introduce an order parameter η to measure the throughput of the network by the critical value of phase transition from free state to congestion state, and analyze the distribution of betweenness centrality and traffic jam. Simulation results show that, compared with the traditional shortest path routing strategy, our method greatly improve the throughput of a network, balance the network traffic load and most of the network nodes are used efficiently. Moreover, the network throughput is maximized under μ = -1, and the transmission performance of the algorithm is independent of the values of α and γ, which indicate the routing strategy is stable and reliable.
Theoretical Analysis and Experimental Investigation on Buckling of FASTMast Deployable Structures
Authors: Jin Yulong , Liu Tao , Lyu Rongxin , Ji Bin , Cui Qifeng
Published: October 2014

FASTMast (Folding Articulated Square Truss Mast) deployable structure is the main bracing structure for the flexible solar array of the international space stations. This study investigates the buckling of FASTMast deployable structures. To this end, the buckling modes and the stiffness characteristics of this structure using the flex batten as an elastic bearing member were theoretically analyzed. The analytical results show that (1) the buckling mode of a FASTMast deployable structure is similar to the elbow joint movement failure when the stiffness of the flex batten is below a critical stiffness value. Once this critical stiffness is reached, the buckling mode takes on the form of Euler buckling. (2) The stiffness of the flex batten is proportional to its cross-sectional second moment of area. Furthermore, an experimental study was carried out to validate the accuracy of the theoretical analysis. The results from experimental work agree fairly well with those from theoretical analysis. The research findings herein are expected to be useful for future studies on similar structures.
RUPTURE MODEL OF INTRACRANIAL SACCULAR ANEURYSMS DUE TO HYPERTENSION
Authors: DAVID GUIDO , NABONG JENNICA RICA
Published: October 2014

The risk of rupture of intracranial saccular aneurysms is one of the leading dilemmas for patients and neurologists. Although the probability of rupture is small, the consequences of rupture are usually fatal or crippling, and a concern for the patient is whether or not to treat an existing aneurysm. In this paper, an idealized model of saccular aneurysms with assumed Fung material behavior was investigated for rupture potential when the stresses exceeded the maximum wall strength of the aneurysm wall. Numerical simulations used various levels of blood pressure, from normal to hypertensive, in order to determine correlations of aneurysm size and risk of rupture. Results showed that hypertensive individuals harboring cerebral aneurysms with a size of at least 6 mm are at risk.
MISSION: POSSIBLE BUT SENSITIVE — KNOWLEDGE PROTECTION MECHANISMS SERVING DIFFERENT PURPOSES
Authors: OLANDER HEIDI , HURMELINNA-LAUKKANEN PIA , VANHALA MIKA
Published: October 2014

Innovations have the potential to create value by generating rents (primary appropriability), or they can be used as background knowledge for further innovations and value creation (generative appropriability). Because these possibilities exist, organisations need to make strategic decisions on knowledge sharing with their partners in collaborative innovation. In best cases, primary and generative appropriability are complementarities rather than alternatives: Knowledge sharing with partners for new innovation could be made safer using formal and informal isolating appropriability mechanisms that improve controllability, thereby preserving rent generation possibilities and simultaneously allowing safe knowledge exchange. We use a quantitative sample of 209 Finnish firms to examine how different formal and informal appropriability mechanisms relate to value capture and creation, and whether these relationships are affected by the strategic goal to reduce imitation of competitors or to improve safe knowledge sharing to partners.
The study of human health effect induced by depth information of stereo vision film
Authors: Wang Xiao , Qian Zhiyu , Xing Lidong , Jin Shuai , Liu Baoyu , Li Zhongqiang , Yin Jianhua
Published: October 2014

The stereo vision results from the interaction between geometrical optics and visual psychology. Large depth will bring discomforts for the results of ghosting and flicker. The relevance of the ratio of jumping out depth (RJD) and electroencephalogram (EEG) gravity frequency (GF) was explored to reflect human health under different three-dimensional (3D) depth information (mainly the negative disparity) displayed on a three-dimensional television (3D-TV) with shutter glasses. EEG was obtained from 10 volunteers when they were watching 3D film segments with different negative disparities. The brain GF map shows that the depth information has a stronger influence on the frontal lobe than on the occipital lobe. For regression analysis, nonlinear curve fittings of GF to RJD in Fp1, F3, O2 and T5 channels were mainly performed when RJD ranged from 0 to 3.4, while linear fittings were performed in some special RJD ranges. It also confirms that RJD above 2.2 may lead to discomfort to human body. Finally, it suggests a suitable RJD range for people to watch from the objective method. The outcomes can be used as a guidance to decrease human discomforts induced by 3D production.
Ornamental stones of the Verbano Cusio Ossola quarry district: characterization of materials, quarrying techniques and history and relevance to local and national heritage
Authors: Dino Giovanna A. , Cavallo Alessandro
Published: October 2014

This paper reports the results of an Interreg Project (OSMATER – Sub-Alpine Observatory Materials Territory Restoration) that investigated the present and historical quarrying and processing activities in the cross-border area between the Ossola Valley (Italy) and the Canton Ticino (Switzerland), and the use of dimension stones in local and national architecture. These materials are in many ways unique for their abundance and lithological variety. In the past, their extraction, processing and application characterized in a decisive way the architectural and constructive culture, both in terms of prestigious architecture and civil buildings, establishing a relationship between ‘stones and culture’, and ‘territory and its resources’. In recent years, many traditions of the quarrying, processing and architectural activities are losing importance and interest is being loss, resulting in a loss of knowledge and historical memory. The loss of this knowledge is likely to become irreversible in the short term, with the disappearance of people and social groups as depositaries of tradition. We conclude that the creation of an ‘observatory’, like OSMATER, is desirable and, indeed, essential if we want to preserve the historical memory of the stone industry of an entire production area.
Constitutive PKA activity is essential for maintaining the excitability and contractility in guinea pig urinary bladder smooth muscle: role of the BK channel
Authors: Xin Wenkuan , Li Ning , Cheng Qiuping , Fernandes Vitor S. , Petkov Georgi V.
Published: October 2014

The elevation of protein kinase A (PKA) activity activates the large-conductance voltage- and Ca2+-activated K+ (BK) channels in urinary bladder smooth muscle (UBSM) cells and consequently attenuates spontaneous phasic contractions of UBSM. However, the role of constitutive PKA activity in UBSM function has not been studied. Here, we tested the hypothesis that constitutive PKA activity is essential for controlling the excitability and contractility of UBSM. We used patch clamp electrophysiology, line-scanning confocal and ratiometric fluorescence microscopy on freshly isolated guinea pig UBSM cells, and isometric tension recordings on freshly isolated UBSM strips. Pharmacological inhibition of the constitutive PKA activity with H-89 or PKI 14–22 significantly reduced the frequency and amplitude of spontaneous transient BK channel currents (TBKCs) in UBSM cells. Confocal and ratiometric fluorescence microscopy studies revealed that inhibition of constitutive PKA activity with H-89 reduced the frequency and amplitude of the localized Ca2+ sparks but increased global Ca2+ levels and the magnitude of Ca2+ oscillations in UBSM cells. H-89 abolished the spontaneous transient membrane hyperpolarizations and depolarized the membrane potential in UBSM cells. Inhibition of PKA with H-89 or KT-5720 also increased the amplitude and muscle force of UBSM spontaneous phasic contractions. This study reveals the novel concept that constitutive PKA activity is essential for controlling localized Ca2+ signals generated by intracellular Ca2+ stores and cytosolic Ca2+ levels. Furthermore, constitutive PKA activity is critical for mediating the spontaneous TBKCs in UBSM cells, where it plays a key role in regulating spontaneous phasic contractions in UBSM.
Dynamic and extensive metabolic state-dependent regulation of cytokine expression and circulating levels
Authors: Petersen Pia S. , Lei Xia , Seldin Marcus M. , Rodriguez Susana , Byerly Mardi S. , Wolfe Andrew , Whitlock Scott , Wong G. William
Published: October 2014

Cytokines play diverse and critical roles in innate and acquired immunity, and several function within the central nervous system and in peripheral tissues to modulate energy metabolism. The extent to which changes in energy balance impact the expression and circulating levels of cytokines (many of which have pleiotropic functions) has not been systematically examined. To investigate metabolism-related changes in cytokine profiles, we used a multiplex approach to assess changes in 71 circulating mouse cytokines in response to acute (fasting and refeeding) and chronic (high-fat feeding) alterations in whole body metabolism. Refeeding significantly decreased serum levels of IL-22, IL-1α, soluble (s)IL-2Rα, and soluble vascular endothelial growth factor receptor 3 (VEGFR3), but markedly increased granulocyte colony-stimulating factor (G-CSF), IL-1β, chemokine (C-C motif) ligand (CCL2), sIL-1RI, lipocalin-2, pentraxin-3, tissue inhibitor of metalloproteinase (TIMP-1), and serum amyloid protein (SAP) relative to the fasted state. Interestingly, only a few of these changes paralleled the alterations in expression of their corresponding mRNAs. Functional studies demonstrated that central delivery of G-CSF increased, whereas IL-22 decreased, food intake. Changes in food intake were not accompanied by acute alterations in orexigenic ( Npy and Agrp) and anorexigenic ( Pomc and Cart) neuropeptide gene expression in the hypothalamus. In the context of chronic high-fat feeding, circulating levels of chemokine (C-X-C) ligand (CXCL1), serum amyloid protein A3 (SAA3), TIMP-1, α1-acid glycoprotein (AGP), and A2M were increased, whereas IL-12p40, CCL4, sCD30, soluble receptor for advanced glycation end products (sRAGE), CCL12, CCL20, CX3CL1, IL-16, IL-22, and haptoglobin were decreased relative to mice fed a control low-fat diet. These results demonstrate that both short- and long-term changes in whole body metabolism extensively alter cytokine expression and circulating levels, thus providing a foundation and framework for further investigations to ascertain the metabolic roles for these molecules in physiological and pathological states.
Diabetic nephropathy is resistant to oral l-arginine or l-citrulline supplementation
Authors: You Hanning , Gao Ting , Cooper Timothy K. , Morris Sidney M. , Awad Alaa S.
Published: October 2014

Our recent publication showed that pharmacological blockade of arginases confers kidney protection in diabetic nephropathy via a nitric oxide (NO) synthase (NOS)3-dependent mechanism. Arginase competes with endothelial NOS (eNOS) for the common substrate l-arginine. Lack of l-arginine results in reduced NO production and eNOS uncoupling, which lead to endothelial dysfunction. Therefore, we hypothesized that l-arginine or l-citrulline supplementation would ameliorate diabetic nephropathy. DBA mice injected with multiple low doses of vehicle or streptozotocin (50 mg/kg ip for 5 days) were provided drinking water with or without l-arginine (1.5%, 6.05 g·kg−1·day−1) or l-citrulline (1.66%, 5.73 g·kg−1·day−1) for 9 wk. Nonsupplemented diabetic mice showed significant increases in albuminuria, blood urea nitrogen, glomerular histopathological changes, kidney macrophage recruitment, kidney TNF-α and fibronectin mRNA expression, kidney arginase activity, kidney arginase-2 protein expression, and urinary oxidative stress along with a significant reduction of nephrin and eNOS protein expression and kidney nitrite + nitrate compared with normal mice after 9 wk of diabetes. Surprisingly, l-arginine or l-citrulline supplementation in diabetic mice did not affect any of these parameters despite greatly increasing kidney and plasma arginine levels. These findings demonstrate that chronic l-arginine or l-citrulline supplementation does not prevent or reduce renal injury in a model of type 1 diabetes.
Corollary discharge inhibition of wind-sensitive cercal giant interneurons in the singing field cricket
Authors: Schöneich Stefan , Hedwig Berthold
Published: October 2014

Crickets carry wind-sensitive mechanoreceptors on their cerci, which, in response to the airflow produced by approaching predators, triggers escape reactions via ascending giant interneurons (GIs). Males also activate their cercal system by air currents generated due to the wing movements underlying sound production. Singing males still respond to external wind stimulation, but are not startled by the self-generated airflow. To investigate how the nervous system discriminates sensory responses to self-generated and external airflow, we intracellularly recorded wind-sensitive afferents and ventral GIs of the cercal escape pathway in fictively singing crickets, a situation lacking any self-stimulation. GI spiking was reduced whenever cercal wind stimulation coincided with singing motor activity. The axonal terminals of cercal afferents showed no indication of presynaptic inhibition during singing. In two ventral GIs, however, a corollary discharge inhibition occurred strictly in phase with the singing motor pattern. Paired intracellular recordings revealed that this inhibition was not mediated by the activity of the previously identified corollary discharge interneuron (CDI) that rhythmically inhibits the auditory pathway during singing. Cercal wind stimulation, however, reduced the spike activity of this CDI by postsynaptic inhibition. Our study reveals how precisely timed corollary discharge inhibition of ventral GIs can prevent self-generated airflow from triggering inadvertent escape responses in singing crickets. The results indicate that the responsiveness of the auditory and wind-sensitive pathway is modulated by distinct CDIs in singing crickets and that the corollary discharge inhibition in the auditory pathway can be attenuated by cercal wind stimulation.
Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network
Authors: Segers L. S. , Nuding S. C. , Ott M. M. , Dean J. B. , Bolser D. C. , O'Connor R. , Morris K. F. , Lindsey B. G.
Published: October 2014

Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that “tonic” pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons.
Behavioral and neuronal recording of the nucleus accumbens in adolescent rats following acute and repetitive exposure to methylphenidate
Authors: Frolov Alexander , Reyes-Vasquez Cruz , Dafny Nachum
Published: October 2014

The nucleus accumbens (NAc) has been shown to play a key role in the brain's response to methylphenidate (MPD). The present study focuses on neuronal recording from this structure. The study postulates that repetitive exposure to the same dose of MPD will elicit in some rats behavioral sensitization and in others tolerance. Furthermore, the study postulates that NAc neuronal activity recorded from animals expressing behavioral tolerance after repetitive MPD exposure will be significantly different from NAc neuronal activity recorded from animals expressing behavioral sensitization after repetitive MPD exposure at doses of 0.6, 2.5, 5.0, and 10.0 mg/kg. To test this, behavioral and neuronal activity was recorded concomitantly from the NAc of freely behaving adolescent rats (postnatal day 40) before and after acute and repetitive administration of four different MPD doses. Comparing the acute MPD effect to the repetitive MPD effect revealed that the acute response to MPD exhibited dose-response characteristics: an increase in behavioral activity correlated with increasing MPD doses. On the other hand, following repetitive MPD exposure, some animals exhibited attenuated behavior (tolerance), while others exhibited further increases in the recorded behavior (sensitization). Moreover, the neuronal activity following repetitive MPD exposure recorded in animals exhibiting behavioral sensitization was significantly different from neuronal activity recorded in animals exhibiting behavioral tolerance. This implies that when studying the effects of repetitive MPD administration on adolescent rats, it is advisable to simultaneously record both neuronal and behavioral activity and to evaluate all data based on the animals' behavioral response to the repetitive MPD exposure.
Humidity sensation, cockroaches, worms, and humans: are common sensory mechanisms for hygrosensation shared across species?
Authors: Filingeri Davide
Published: October 2014

Although the ability to detect humidity (i.e., hygrosensation) represents an important sensory attribute in many animal species (including humans), the neurophysiological and molecular bases of such sensory ability remain largely unknown in many animals. Recently, Russell and colleagues (Russell J, Vidal-Gadea AG, Makay A, Lanam C, Pierce-Shimomura JT. Proc Natl Acad Sci USA 111: 8269–8274, 2014) provided for the first time neuromolecular evidence for the sensory integration of thermal and mechanical sensory cues which underpin the hygrosensation strategy of an animal (i.e., the free-living roundworm Caenorhabditis elegans) that lacks specific sensory organs for humidity detection (i.e., hygroreceptors). Due to the remarkable similarities in the hygrosensation transduction mechanisms used by hygroreceptor-provided (e.g., insects) and hygroreceptor-lacking species (e.g., roundworms and humans), the findings of Russell et al. highlight potentially universal mechanisms for humidity detection that could be shared across a wide range of species, including humans.
Endosonographic Features of Histologically Proven Gastric Ectopic Pancreas
Authors: Chou Jen-Wei , Cheng Ken-Sheng , Ting Chun-Fu , Feng Chun-Lung , Lin Yu-Ta , Huang Wen-Hsin
Published: October 2014

Gastric ectopic pancreas is an uncommon developmental anomaly and its histological diagnosis is usually difficult by using a conventional biopsy forceps. In the literature, most cases of gastric ectopic pancreas were usually diagnosed by gross pattern during endoscopic examination or features of endoscopic ultrasound. In contrast, this disease was seldom diagnosed by histology in clinical practice. Although the typical endoscopic ultrasonographic features of ectopic pancreas include heterogeneous echogenicity, indistinct borders, and a location within 2 or more layers, it can also exhibit hypoechoic homogeneous echogenicity and a distinct border within the fourth sonographic layer (muscularis propria) similar to the endoscopic ultrasonographic features of gastrointestinal stromal tumors. In our study, we found that 53% of gastric ectopic pancreas originated within the fourth sonographic layer, demonstrating hypoechoic, homogeneous echogenicity, and distinct borders. Therefore, recognizing endoscopic ultrasonographic features, combining with deep biopsy, endoscopic ultrasound-guided fine needle aspiration/core needle biopsy can prevent conducting unnecessary resection. Surgical resection is the mainstay treatment for symptomatic gastric ectopic pancreas, but endoscopic resection using endoscopic mucosal resection or endoscopic submucosal dissection technique provides an alternative method of removing superficial-type and deep-type gastric ectopic pancreas.