bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Metapneumovirus SH and G Glycoproteins Inhibit Macropinocytosis-Mediated Entry into Human Dendritic Cells and Reduce CD4
+
T Cell Activation
Authors: Le Nouën Cyril , Hillyer Philippa , Brock Linda G. , Winter Christine C. , Rabin Ronald L. , Collins Peter L. , Buchholz Ursula J.
Published: March 2014

Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to HMPV is incomplete and short-lived. We used gene-deletion viruses to evaluate the role of the attachment G and small hydrophobic SH glycoproteins on virus uptake by primary human monocyte-derived dendritic cells (MDDC)
in vitro
and on subsequent MDDC maturation and activation of autologous T cells. HMPV with deletion of G and SH (ΔSHG) exhibited increased infectivity but had little effect on MDDC maturation. However, MDDC stimulated with ΔSHG induced increased proliferation of autologous Th1-polarized CD4
+
T cells. This effect was independent of virus replication. Increased T cell proliferation was strictly dependent on contact between virus-stimulated MDDC and CD4
+
T cells. Confocal microscopy revealed that deletion of SH and G was associated with an increased number of immunological synapses between memory CD4
+
T cells and virus-stimulated MDDC. Uptake of HMPV by MDDC was found to be primarily by macropinocytosis. Uptake of wild-type (WT) virus was reduced compared to that of ΔSHG, indicative of inhibition by the SH and G glycoproteins. In addition, DC-SIGN-mediated endocytosis provided a minor alternative pathway that depended on SH and/or G and thus operated only for WT. Altogether, our results show that SH and G glycoproteins reduce the ability of HMPV to be internalized by MDDC, resulting in a reduced ability of the HMPV-stimulated MDDC to activate CD4
+
T cells. This study describes a previously unknown mechanism of virus immune evasion.

IMPORTANCE
Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to HMPV is incomplete and short-lived. We found that HMPV attachment G and small hydrophobic SH glycoproteins reduce the ability of HMPV to be internalized by macropinocytosis into human dendritic cells (DC). This results in a reduced ability of the HMPV-stimulated DC to activate Th1-polarized CD4
+
T cells. These results contribute to a better understanding of the nature of incomplete protection against this important human respiratory virus, provide new information on the entry of HMPV into human cells, and describe a new mechanism of virus immune evasion.
A Unique N-Terminal Sequence in the Carnation Italian ringspot virus p36 Replicase-Associated Protein Interacts with the Host Cell ESCRT-I Component Vps23
Authors: Richardson Lynn G. L. , Clendening Eric A. , Sheen Hyukho , Gidda Satinder K. , White K. Andrew , Mullen Robert T.
Published: March 2014

Like most positive-strand RNA viruses, infection by plant tombusviruses results in extensive rearrangement of specific host cell organelle membranes that serve as the sites of viral replication. The tombusvirus
Tomato bushy stunt virus
(TBSV) replicates within spherules derived from the peroxisomal boundary membrane, a process that involves the coordinated action of various viral and cellular factors, including constituents of the endosomal sorting complex required for transport (ESCRT). ESCRT is comprised of a series of protein subcomplexes (i.e., ESCRT-0 -I, -II, and -III) that normally participate in late endosome biogenesis and some of which are also hijacked by certain enveloped retroviruses (e.g., HIV) for viral budding from the plasma membrane. Here we show that the replication of
Carnation Italian ringspot virus
(CIRV), a tombusvirus that replicates at mitochondrial membranes also relies on ESCRT. In plant cells, CIRV recruits the ESCRT-I protein, Vps23, to mitochondria through an interaction that involves a unique region in the N terminus of the p36 replicase-associated protein that is not conserved in TBSV or other peroxisome-targeted tombusviruses. The interaction between p36 and Vps23 also involves the Vps23 C-terminal steadiness box domain and not its N-terminal ubiquitin E2 variant domain, which in the case of TBSV (and enveloped retroviruses) mediates the interaction with ESCRT. Overall, these results provide evidence that CIRV uses a unique N-terminal sequence for the recruitment of Vps23 that is distinct from those used by TBSV and certain mammalian viruses for ESCRT recruitment. Characterization of this novel interaction with Vps23 contributes to our understanding of how CIRV may have evolved to exploit key differences in the plant ESCRT machinery.

IMPORTANCE
Positive-strand RNA viruses replicate their genomes in association with specific host cell membranes. To accomplish this, cellular components responsible for membrane biogenesis and modeling are appropriated by viral proteins and redirected to assemble membrane-bound viral replicase complexes. The diverse pathways leading to the formation of these replication structures are poorly understood. We have determined that the cellular ESCRT system that is normally responsible for mediating late endosome biogenesis is also involved in the replication of the tombusvirus
Carnation Italian ringspot virus
(CIRV) at mitochondria. Notably, CIRV recruits ESCRT to the mitochondrial outer membrane via an interaction between a unique motif in the viral protein p36 and the ESCRT component Vps23. Our findings provide new insights into tombusvirus replication and the virus-induced remodeling of plant intracellular membranes, as well as normal ESCRT assembly in plants.
Carotid stent infection: a rare but potentially fatal complication of carotid artery stenting
Authors: Son Seungnam , Choi Nack-Cheon , Choi Dae Seob , Cho Oh Hyun
Published: March 2014

Infections involving endovascular devices are rare and, to our knowledge, only three cases of infection with an inserted carotid stent have ever been reported. A 68-year-old man underwent carotid artery stenting (CAS) of the left proximal internal carotid artery. Two days after CAS the patient developed a high fever and investigation showed that the inserted carotid stent was infected. The infection could not be controlled despite adequate antibiotic therapy. Eventually a rupture of the carotid artery occurred and the patient underwent emergency resection of the left carotid bifurcation in addition to stent removal and reconstruction with a saphenous vein interposition graft. The patient recovered fully without any neurological sequelae.
Feasibility of aerosol drug delivery to sleeping infants: a prospective observational study
Authors: Amirav Israel , Newhouse Michael T , Luder Anthony , Halamish Asaf , Omar Hamza , Gorenberg Miguel
Published: March 2014

Objectives

Delivery of inhaled medications to infants is usually very demanding and is often associated with crying and mask rejection. It has been suggested that aerosol administration during sleep may be an attractive alternative. Previous studies in sleeping children were disappointing as most of the children awoke and rejected the treatment. The SootherMask (SM) is a new, gentle and innovative approach for delivering inhaled medication to infants and toddlers. The present pilot study describes the feasibility of administering inhaled medications during sleep using the SM.

Design

Prospective observational study.

Setting

Out patients.

Participants

13 sleeping infants with recurrent wheezing who regularly used pacifiers and were <12 months old.

Intervention

Participants inhaled technetium99mDTPA-labelled normal saline aerosol delivered via a Respimat Soft Mist Inhaler (SMI) (Boehringer-Ingelheim, Germany) and SM + InspiraChamber (IC; InspiRx Inc, New Jersey, USA).

Outcomes

The two major outcomes were the acceptability of the treatment and the lung deposition (per cent of emitted dose).

Results

All infants who fulfilled the inclusion criteria successfully received the SM treatment during sleep without difficulty. Mean lung deposition (±SD) averaged 1.6±0.5% in the right lung.

Conclusions

This study demonstrated that the combination of Respimat, IC and SM was able to administer aerosol therapy to all the sleeping infants who were regular pacifier users with good lung deposition. Administration of aerosols during sleep is advantageous since all the sleeping children accepted the mask and ensuing aerosol therapy under these conditions, in contrast to previous studies in which there was frequent mask rejection using currently available devices.

Clinical Trial Registry

NCT01120938.
Identifying the key elements of an education package to up-skill multidisciplinary adult specialist palliative care teams caring for young adults with life-limiting conditions: an online Delphi study
Authors: Sivell Stephanie , Lidstone Victoria , Taubert Mark , Thompson Catherine , Nelson Annmarie
Published: March 2014

Objectives

To collect the views of experts to inform the development of an education package for multidisciplinary adult specialist palliative care (SPC) teams caring for young people with life-limiting conditions.

Methods

A modified online Delphi process collated expert opinion on format, delivery and content of an education package to up-skill adult SPC teams. Round 1 participants (n=44) answered free-text questions, generating items for Round 2. In Round 2, 68 participants rated the extent to which they agreed/disagreed with the items on 5-point Likert-type scales. Median and mean scores assessed the importance of each item. IQR scores assessed level of consensus for each item; items lacking consensus were rerated by 35 participants in Round 3.

Results

In the Delphi, consensus was reached on a range of suggested formats, on who should deliver the training, and on several clinical, psychosocial and practical topics.

Conclusions

Development of a continuous/rolling programme of education, tailored for content and mode of delivery and incorporated into working practice is recommended. As a direct outcome of the results of this study, a series of six linked study days has been established, focusing specifically on the issues around caring for young adults with life-limiting conditions and palliative care needs.
A reconsideration of the correlation between veteran status and firearm suicide in the general population
Authors: Hoffmire Claire A , Bossarte Robert M
Published: March 2014

Background

The relationship between veteran status and firearm suicide has been evaluated previously, but multiple sources of bias limit conclusions. This study aimed to clarify the relationship between a history of military service and firearm suicide.

Methods

Data obtained from suicide death certificates from nine states (1999–2009) were analysed. History of military service was validated using data obtained from the Department of Veterans Affairs and Department of Defense. Modified Poisson Regression with robust SEs was used to compute adjusted prevalence ratios for the common outcome of firearm use among suicide decedents.

Results

Male veteran suicide decedents were 6% more likely to use firearms, and female veteran suicide decedents were 18% more likely to use firearms compared with their non-veteran peers.

Conclusions

Prior estimates based on logistic regression and death certificate reporting of veteran status may have overestimated the relationship between veteran status and firearm use among suicide decedents.
How well do principal diagnosis classifications predict disability 12 months postinjury?
Authors: Gabbe Belinda J , Simpson Pam M , Lyons Ronan A , Polinder Suzanne , Rivara Frederick P , Ameratunga Shanthi , Derrett Sarah , Haagsma Juanita , Harrison James E
Published: March 2014

Background

The application of disability weights by nature of injury is central to the calculation of disability-adjusted life years (DALYs). Such weights should represent injury diagnosis groups that demonstrate homogeneity in disability outcomes. Existing classifications have not used empirical data in their development to inform groups that are homogeneous for disability outcomes, limiting the capacity to make informed recommendations for best practice in measuring injury burden.

Methods

The Validating and Improving injury Burden Estimates (Injury-VIBES) Study includes pooled data from over 30 000 injured participants recruited to six cohort studies. The International Classification of Disease 10th Revision (ICD-10) diagnosis codes were mapped to existing injury burden study groupings and prediction models were developed to measure the capacity of the injury groupings and ICD-10 diagnoses to predict disability outcomes at 12 months. Models were adjusted for age, gender and data source and investigated for discrimination using area under the receiver operating characteristic curve (AUC) and calibration using Hosmer–Lemeshow statistics and calibration curves.

Results

Discrimination and calibration of models varied depending on the outcome measured. Models using full four-character ICD-10 diagnosis codes, rather than groupings of codes, demonstrated the highest discrimination ranging from an AUC (95% CI) of 0.627 (0.618 to 0.635) for the pain or discomfort item of the EQ-5D to 0.847 (0.841 to 0.853) for the extended Glasgow Outcome Scale independent living outcome. However, gain over other groupings was marginal.

Conclusions

Prediction performance was best for measures of function such as independent living, mobility and self-care. The classifications were poorer predictors of anxiety/depression and pain/discomfort. There was no clearly superior classification.
Evaluating community engagement as part of the public health system
Authors: South Jane , Phillips Gemma
Published: March 2014

Community participation and leadership is a central tenet of public health policy and practice. Community engagement approaches are used in a variety of ways to facilitate participation, ranging from the more utilitarian, involving lay delivery of established health programmes, to more empowerment-oriented approaches. Evaluation methods within public health, adapted from clinical medicine, are most suited to evaluating community engagement as an ‘intervention’, in the utilitarian sense, focusing on the health impacts of professionally determined programmes. However, as communities are empowered and professional control is relinquished, it is likely to be harder to capture the full effects of an intervention and so the current evidence base is skewed away from knowledge about the utility of these approaches. The aim of this paper is to stimulate debate on the evaluation of community engagement. Building on current understandings of evaluation within complex systems, the paper argues that what is needed is a paradigm shift from viewing the involvement of communities as an errant form of public health action, to seeing communities as an essential part of the public health system. This means moving from evaluation being exclusively focused on the linear causal chain between the intervention and the target population, to seeking to build understanding of whether and how the lay contribution has impacted on the social determinants of health, including the system through which the intervention is delivered. The paper proposes some alternative principles for the evaluation of community engagement that reflect a broader conceptualisation of the lay contribution to public health.
Mortality rate of silky sharks (Carcharhinus falciformis) caught in the tropical tuna purse seine fishery in the Indian Ocean
Authors: Poisson François , Filmalter John David , Vernet Anne-Lise , Dagorn Laurent
Published: March 2014

Scientists aboard French purse seine vessels recorded the number and condition of silky sharks (Carcharhinus falciformis) caught during three fishing cruises in the Indian Ocean. A sample of 31 individuals that showed signs of life were tagged with satellite tags to investigate their postrelease mortality. The majority of individuals (95%) were brought on board using the brailer. Combining the proportion of sharks that were dead (72%) and the mortality rate of those released (48%), the overall mortality rate of brailed individuals was 85%. Few individuals (5%) were not brailed as they were entangled and landed during the hauling process. The survival rate of these individuals was high, with an overall mortality rate of meshed individuals of 18%. The combination of these two categories led to an overall mortality rate of 81%. This high value reflects the harsh conditions encountered by sharks during the purse seine fishing process. Consequently, methods that prevent sharks being brought on board are a priority for future investigations, but good handling practices should also be promoted as they could reduce mortality by at least 19%.
Planting stock type and seasonality of simulated browsing affect regeneration establishment ofQuercus rubra
Authors: Woolery Phillip O. , Jacobs Douglass F.
Published: March 2014

Animal herbivory is a major limiting factor to successful oak (Quercus spp.) regeneration. Although bare-root seedlings are the most commonly used nursery stock type for oak plantings in the eastern United States, container seedlings may better resist planting stress and help enable seedlings to overcome browsing pressure. Four stock types (1 + 0 bare-root seedlings and seedlings in 164, 336, and 520 mL containers) of northern red oak (Quercus rubra L.) were planted on two reforestation sites in Indiana, USA, which were fenced to exclude white-tailed deer (Odocoileus virginianus Zimmerman). Seedlings were then subjected to three simulated browsing treatments (control unclipped, dormant clipped, and summer clipped). Container seedlings exhibited higher relative growth rates on both sites; for example, at one site, control seedlings in 336 mL containers had relative height growth of 558% compared with 79% for bare-root control seedlings. On both sites, summer-browsed seedlings of all stock types had negligible height growth, and summer browsing reduced survival at one site by 23% for all stock types compared with control seedlings. Browsing of seedlings during the dormant period did not affect growth for any stock type. Container seedlings may help facilitate rapid establishment of planted oak seedlings, but browse protection is necessary to ensure oak regeneration success in areas of large populations of deer.
Coccidial dispersion acrosstrans- andcis-Andean antbirds (Passeriformes: Thamnophilidae):Isospora sagittulae(Apicomplexa: Eimeriidae) from nonsympatric hosts
Authors: Berto B.P. , Lopes B.doB. , Melinski R.D. , de Souza A.H.N. , Ribas C.C. , de Abreu F.H.T. , Ferreira I. , Lopes C.W.G.
Published: March 2014

Isospora sagittulae McQuistion and Capparella, 1992 (Protozoa: Apicomplexa: Eimeriidae) is reported from White-throated Antbirds (Gymnopithys salvini (Berlepsch, 1901)) and from Common Scale-backed Antbirds (Willisornis poecilinotus (Cabanis, 1847)), which are thamnophilid birds from the Brazilian Amazon. Its oocysts are ovoidal to ellipsoidal, 28.4 μm × 22.4 μm, with smooth, bilayered wall, 1.1 μm. Micropyle and oocyst residuum are absent, but one to three polar granules are present. Sporocysts are subspherical to ovoidal, 15.0 μm × 12.6 μm. Stieda body thin and flattened and substieda body triangular to round. Sporocyst residuum composed of scattered granules. Sporozoites with refractile body and nucleus. This coccidium was originally described from the Spotted Antbird (Hylophylax naevioides (Lafresnaye, 1847)), a trans-Andean antbird that is not sympatric with G. salvini and W. poecilinotus, which are cis-Andean antbirds from lowland Amazon forest; therefore, this current study presents some assumptions to explain the dispersion of I. sagittulae among antbird species.
Where have all the Goldstone bosons gone?
Authors: Guralnik G. S. , Hagen C. R.
Published: March 2014

According to a commonly held view of spontaneously broken symmetry in gauge theories, troublesome Nambu–Goldstone bosons are effectively eliminated by turning into longitudinal modes of a massive vector meson. This note shows that, this is not in fact, a consistent view of the role of Nambu–Goldstone bosons in such theories. These particles necessarily appear as gauge excitations, whenever they are formulated in a manifestly covariant gauge. The radiation gauge provides therefore the dual advantage of circumventing the Goldstone theorem and making evident the disappearance of these particles from the physical spectrum.
ACTIVE CONTOURS DRIVEN BY LOCAL INTENSITY AND LOCAL GRADIENT FITTING ENERGIES
Authors: YUAN JIANJUN , WANG JIANJUN , LIU LIPEI
Published: March 2014

This paper presents a new local region-based and local gradient-based active contour model in a variational level set formulation for image segmentation. The model consists of three parts: the local region term, the local gradient term and the regularization term. The local region term is insensitive to noise, while the local gradient term has better capability of localization than the local region. The energy minimization is achieved by the level set evolution in an iterative strategy. In each iteration, the local intensity and local gradient are updated and fed into the level set evolution. Comparative experiments show that our model achieves the better performance on the ultrasound images with noise and low signal-to-noise ratio than the local binary fitting (LBF) energy model.
Kinetic evolution of the glasma and thermalization in heavy-ion collisions
Authors: Huang Xu-Guang , Liao Jinfeng
Published: March 2014

In relativistic heavy-ion collisions, a highly occupied gluonic matter is created shortly after initial impact, which is in a nonthermal state and often referred to as the Glasma. Successful phenomenology suggests that the glasma evolves rather quickly toward the thermal quark–gluon plasma (QGP) and a hydrodynamic behavior emerges at a very early time ~ô(1) fm/c. Exactly how such "apparent thermalization" occurs and connects the initial conditions to the hydrodynamic onset, remains a significant challenge for theory as well as phenomenology. We briefly review various ideas and recent progress in understanding the approach of the glasma to the thermalized QGP, with an emphasis on the kinetic theory description for the evolution of such far-from-equilibrium and highly overpopulated, thus weakly-coupled yet strongly interacting glasma.
PEOPLE WATCH
Authors: Lim Rachel
Published: March 2014

Providing for Emerging Markets: A Chat with Raman Singh from Mundipharma.
Green Synthesis and Characterization of Silver Nanoparticles for Antimicrobial Activity Against Burn Wounds Contaminating Bacteria
Authors: Rout Anandini , Jena Padan K. , Sahoo Debasish , Parida Umesh K. , Bindhani Birendra K.
Published: March 2014

Silver nanoparticles ( AgNPs ) were prepared from the plant extract of N. arbor-tristis under atmospheric conditions through green synthesis and characterized by various physicochemical techniques like UV-Visible spectroscopy, IR Spectra, energy dispersive X-ray spectrometry (EDS), X-ray diffraction and transmission electron microscopy (TEM) and the results confirmed the synthesis of homogeneous and stable AgNPs by the plant extracts. The antimicrobial activity of AgNPs was investigated against most common bacteria found in burn wound Staphylococcus epidermidis and Pseudomonas aeruginosa. In these tests, Mueller Hinton agar plates were used with AgNPs of various concentrations, supplemented in liquid systems. P. aeruginosa was inhibited at the low concentration of AgNPs , whereas the growth-inhibitory effect on S. epidermidis was mild. These results suggest that AgNPs can be used as effective growth inhibitors of various microorganisms, making them applicable to diverse medical devices and antimicrobial control systems.
EFFECTS OF TiO2 PARTICLE SIZE ON THE PERFORMANCE OF DYE-SENSITIZED SOLAR CELLS USING IONIC LIQUID ELECTROLYTES
Authors: ITO SEIGO , MURAKAMI TAKUROU N. , ZAKEERUDDIN SHAIK M. , YAZAWA TETSUO , MIZUNO MASAO , KAYAMA SUSUMU , GRÄTZEL MICHAEL
Published: March 2014

Different-sized nanocrystalline- TiO 2 particles have been used for the optimization of photovoltaic effects of dye-sensitized solar cells (DSCs) using an ionic-liquid (IL) electrolyte. Ru dye (Z907) was used for the IL-DSC optimization. The TiO 2 nanoparticle sizes and the thickness of nanocrystalline- TiO 2 electrodes ranged from 13 nm to 81 nm and 2 μm to 23 μm, respectively. The particle size of the nanocrystalline TiO 2 film greatly affected the photovoltaic characteristics, particularly for the IL electrolyte due to limitation of the photocurrent by [Formula: see text]-diffusion. The optimized electrode for IL-DSC had a 15 μm thickness using a 27 nm diameter of nanocrystalline- TiO 2 particles. In order to characterize the effect of the TiO 2 particle size on the photovoltaic effects of IL-DSCs, a scanning electron micrograph (surface and cross section of nanoparticles), BET specific surface area analysis, pore-size distribution analysis, photocurrent transient measurements, haze spectroscopy, photovoltaic measurements, incident-photon-to-current conversion efficiency spectroscopy and impedance measurement have been used.
Investigating the effects of Pentoxifylline on human breast cancer cells using Raman spectroscopy
Authors: Goel Peeyush N. , Singh S. P. , Murali Krishna C. , Gude R. P.
Published: March 2014

Breast cancer is one of the leading causes of cancer-related deaths in a global scenario. In the present study, biochemical changes exerted upon Pentoxifylline (PTX) treatment had been appraised in human breast cancer cells using Raman spectroscopy. There are no clinically approved methods to monitor such therapeutic responses available. The spectral profiling is suggestive of changes in DNA, protein and lipid contents showing a linear relationship with drug dosage. Further, multivariate analysis using principal-component based linear-discriminant-analysis (PC-LDA) was employed for classifying the control and the PTX treated groups. These findings support the feasibility of Raman spectroscopy as an alternate/adjunct label-free, objective method for monitoring drug-induced modifications against breast cancer cells.
The extremal problems on the inertia of weighted bicyclic graphs
Authors: Deng Shibing , Li Shuchao , Song Feifei
Published: March 2014

Let Gw be a weighted graph. The number of the positive, negative and zero eigenvalues in the spectrum of Gw are called positive inertia index, negative inertia index and nullity of Gw, and denoted by i+(Gw), i-(Gw), i0(Gw), respectively. In this paper, sharp lower bound on the positive (respectively, negative) inertia index of weighted bicyclic graphs of order n with pendant vertices is obtained. Moreover, all the weighted bicyclic graphs of order n with at most two positive, two negative and at least n - 4 zero eigenvalues are identified, respectively.
Functional adaptation of bovine mesenteric lymphatic vessels to mesenteric venous hypertension
Authors: Quick Christopher M. , Criscione John C. , Kotiya Akhilesh , Dongaonkar Ranjeet M. , Hardy Joanne , Wilson Emily , Gashev Anatoliy A. , Laine Glen A. , Stewart Randolph H.
Published: March 2014

Lymph flow is the primary mechanism for returning interstitial fluid to the blood circulation. Currently, the adaptive response of lymphatic vessels to mesenteric venous hypertension is not known. This study sought to determine the functional responses of postnodal mesenteric lymphatic vessels. We surgically occluded bovine mesenteric veins to create mesenteric venous hypertension to elevate mesenteric lymph flow. Three days after surgery, postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 7) and sham surgery (Sham; n = 6) group animals were evaluated and compared. Contraction frequency (MVH: 2.98 ± 0.75 min−1; Sham: 5.42 ± 0.81 min−1) and fractional pump flow (MVH: 1.14 ± 0.30 min−1; Sham: 2.39 ± 0.32 min−1) were significantly lower in the venous occlusion group. These results indicate that postnodal mesenteric lymphatic vessels adapt to mesenteric venous hypertension by reducing intrinsic contractile activity.
OMA1 mediates OPA1 proteolysis and mitochondrial fragmentation in experimental models of ischemic kidney injury
Authors: Xiao Xiao , Hu Yanzhong , Quirós Pedro M. , Wei Qingqing , López-Otín Carlos , Dong Zheng
Published: March 2014

Acute kidney injury (AKI) is associated with mitochondrial fragmentation, which contributes to mitochondrial damage and tubular cell apoptosis. Mitochondrial fragmentation involves the cleavage of both mitochondrial outer and inner membranes. Cleavage of the outer membrane results from Drp-1-mediated fission activation and Bak-promoted fusion arrest, but the molecular mechanism of inner membrane cleavage remains elusive. OMA1-mediated proteolysis of OPA1, a key inner membrane fusion protein, was recently suggested to account for inner membrane cleavage during cell stress. In this study, we determined the role of OMA1 in OPA1 proteolysis and mitochondrial fragmentation in experimental models of ischemic AKI. In ATP-depletion injury, knockdown of OMA1 suppressed OPA1 proteolysis, mitochondrial fragmentation, cytochrome c release, and consequent apoptosis in renal proximal tubular cells. In mice, OMA1 deficiency prevented ischemic AKI as indicated by better renal function, less tubular damage, and lower apoptosis. OPA1 proteolysis and mitochondrial injury during ischemic AKI were ameliorated in OMA1-deficient mice. Thus, OMA1-mediated OPA1 proteolysis plays an important role in the disruption of mitochondrial dynamics in ischemic AKI.
Self-motion improves head direction cell tuning
Authors: Shinder Michael E. , Taube Jeffrey S.
Published: March 2014

Head direction (HD) cells respond when an animal faces a particular direction in the environment and form the basis for the animal's perceived directional heading. When an animal moves through its environment, accurate updating of the HD signal is required to reflect the current heading, but the cells still maintain a representation of HD even when the animal is motionless. This finding suggests that the HD system holds its current state in the absence of input, a view that we tested by rotating a head-restrained rat in the presence of a prominent visual landmark and then stopping it suddenly when facing the cell's preferred firing direction (PFD). Firing rates were unchanged for the first 100 ms, but then progressively decreased over the next 4 s and stabilized at ∼42% of their initial values. When the rat was stopped facing away from the PFD, there was no initial effect of braking, but the firing rate then increased steadily over 4 s and plateaued at ∼14% of its peak firing rate, substantially above initial background firing rates. In experiment 2, the rat was serially placed facing one of eight equidistant directions over 360° and held there for 30 s. Compared with the cell's peak firing rate during a passive rotation session, firing rates were reduced (51%) for in-PFD directions and increased (∼300%) from background levels for off-PFD directions, values comparable to those observed in the braking protocol. These differential HD cell responses demonstrate the importance of self-motion to the HD signal integrity.
Long-latency, inhibitory spinal pathway to ankle flexors activated by homonymous group 1 afferents
Authors: Zewdie Ephrem T. , Roy Francois D. , Okuma Yoshino , Yang Jaynie F. , Gorassini Monica A.
Published: March 2014

Inhibitory feedback from sensory pathways is important for controlling movement. Here, we characterize, for the first time, a long-latency, inhibitory spinal pathway to ankle flexors that is activated by low-threshold homonymous afferents. To examine this inhibitory pathway in uninjured, healthy participants, we suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50, and 60 ms earlier and at intensities of 0.5–0.7 times motor threshold (average suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below M-wave and H-reflex threshold, it produced a long-latency inhibition of background muscle activity, approximately 65–115 ms after the CPN stimulation, a time period that overlapped with the test MEP. However, not all of the MEP suppression could be accounted for by this decrease in background muscle activity. Evoked responses from direct activation of the corticospinal tract, at the level of the brain stem or thoracic spinal cord, were also suppressed by low-threshold CPN stimulation. Our findings suggest that low-threshold muscle and cutaneous afferents from the CPN activate a long-latency, homonymous spinal inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from spinal networks, activated by low-threshold homonymous afferents, helps regulate the activation of flexor motoneurons by the corticospinal tract.
Depressed GABA and glutamate synaptic signaling by 5-HT1Areceptors in the nucleus tractus solitarii and their role in cardiorespiratory function
Authors: Ostrowski Tim D. , Ostrowski Daniela , Hasser Eileen M. , Kline David D.
Published: March 2014

Serotonin (5-HT), and its 5-HT1Areceptor (5-HT1AR) subtype, is a powerful modulator of the cardiorespiratory system and its sensory reflexes. The nucleus tractus solitarii (nTS) serves as the first central station for visceral afferent integration and is critical for cardiorespiratory reflex responses. However, the physiological and synaptic role of 5-HT1ARs in the nTS is relatively unknown. In the present study, we examined the distribution and modulation of 5-HT1ARs on cardiorespiratory and synaptic parameters in the nTS. 5-HT1ARs were widely distributed to cell bodies within the nTS but not synaptic terminals. In anesthetized rats, activation of 5-HT1ARs by microinjection of the 5-HT1AR agonist 8-OH-DPAT into the caudal nTS decreased minute phrenic neural activity via a reduction in phrenic amplitude. In brain stem slices, 8-OH-DPAT decreased the amplitude of glutamatergic tractus solitarii-evoked excitatory postsynaptic currents, and reduced overall spontaneous excitatory nTS network activity. These effects persisted in the presence of GABAAreceptor blockade and were antagonized by coapplication of 5-HT1AR blocker WAY-100135. 5-HT1AR blockade alone had no effect on tractus solitarii-evoked excitatory postsynaptic currents, but increased excitatory network activity. On the other hand, GABAergic nTS-evoked inhibitory postsynaptic currents did not change by activation of the 5-HT1ARs, but spontaneous inhibitory nTS network activity decreased. Blocking 5-HT1ARs tended to increase nTS-evoked inhibitory postsynaptic currents and inhibitory network activity. Taken together, 5-HT1ARs in the caudal nTS decrease breathing, likely via attenuation of afferent transmission, as well as overall nTS network activity.
Task-dependent control of the jaw during food splitting in humans
Authors: Johansson Anders S. , Westberg Karl-Gunnar , Edin Benoni B.
Published: March 2014

Although splitting of food items between the incisors often requires high bite forces, rarely do the teeth harmfully collide when the jaw quickly closes after split. Previous studies indicate that the force-velocity relationship of the jaw closing muscles principally explains the prompt dissipation of jaw closing force. Here, we asked whether people could regulate the dissipation of jaw closing force during food splitting. We hypothesized that such regulation might be implemented via differential recruitment of masseter muscle portions situated along the anteroposterior axis because these portions will experience a different shortening velocity during jaw closure. Study participants performed two different tasks when holding a peanut-half stacked on a chocolate piece between their incisors. In one task, they were asked to split the peanut-half only (single-split trials) and, in the other, to split both the peanut and the chocolate in one action (double-split trials). In double-split trials following the peanut split, the intensity of the tooth impact on the chocolate piece was on average 2.5 times greater than in single-split trials, indicating a substantially greater loss of jaw closing force in the single-split trials. We conclude that control of jaw closing force dissipation following food splitting depends on task demands. Consistent with our hypothesis, converging neurophysiological and morphometric data indicated that this control involved a differential activation of the jaw closing masseter muscle along the anteroposterior axis. These latter findings suggest that the regulation of jaw closing force after sudden unloading of the jaw exploits masseter muscle compartmentalization.
On the Genesis of Neuroblastoma and Glioma
Authors: de Weille Jan
Published: March 2014

As the emergence of cancer is most frequent in proliferating tissues, replication errors are considered to be at the base of this disease. This review concentrates mainly on two neural cancers, neuroblastoma and glioma, with completely different backgrounds that are well documented with respect to their ontogeny. Although clinical data on other cancers of the nervous system are available, usually little can be said about their origins. Neuroblastoma is initiated in the embryo at a moment when the nervous system (NS) is in full expansion and occasionally genomic damage can lead to neoplasia. Glioma, to the contrary, occurs in the adult brain supposed to be mostly in a postmitotic state. According to current consensus, neural stem cells located in the subventricular zone (SVZ) in the adult are thought to accumulate enough genomic mutations to diverge on a carcinogenic course leading to diverse forms of glioma. After weighing the pros and cons of this current hypothesis in this review, it will be argued that this may be improbable, yielding to the original old concept of glial origin of glioma.
Potential Association between Breakfast Skipping and Concomitant Late-Night-Dinner Eating with Metabolic Syndrome and Proteinuria in the Japanese Population
Authors: Kutsuma Ayano , Nakajima Kei , Suwa Kaname
Published: March 2014

Skipping breakfast is considered to be an unhealthy eating habit linked to predispositions to obesity and type 2 diabetes. Because eating dinner late at night can elicit subsequent breakfast skipping, we investigated if skipping breakfast concomitant with late-night-dinner eating (LNDE) was associated with metabolic syndrome (MetS) and proteinuria in the general Japanese population. We examined self-reported habitual breakfast skipping and LNDE, MetS (modified ATP-III criteria), and proteinuria in a cross-sectional study of 60,800 Japanese adults aged 20–75 years. A total of 14,068 subjects (23.1%) skipped breakfast, of whom approximately half (52.8%) skipped breakfast alone (without LNDE). The percentages of subjects who skipped breakfast showed a J-shaped relationship with body mass index (BMI). Multivariate logistic regression analysis showed that skipping breakfast concomitant with LNDE (n= 6,645) was significantly associated with MetS and proteinuria, even after adjusting for relevant confounders (odds ratio (95% CI), 1.17 (1.08–1.28),P=0.0003, and 1.37 (1.24–1.52),P<0.0001, resp.). Skipping breakfast alone and LNDE alone were not associated with MetS and proteinuria, respectively. In conclusion, habitual breakfast skipping concomitant with LNDE may represent poorer eating behavior than skipping breakfast alone, associated with MetS, asymptomatic proteinuria, obesity, and low body weight in the general Japanese population.
FittingC2Continuous Parametric Surfaces to Frontiers Delimiting Physiologic Structures
Authors: Bayer Jason D. , Epstein Matthew , Beaumont Jacques
Published: March 2014

We present a technique to fitC2continuous parametric surfaces to scattered geometric data points forming frontiers delimiting physiologic structures in segmented images. Such mathematical representation is interesting because it facilitates a large number of operations in modeling. While the fitting ofC2continuous parametric curves to scattered geometric data points is quite trivial, the fitting ofC2continuous parametric surfaces is not. The difficulty comes from the fact that each scattered data point should be assigned a unique parametric coordinate, and the fit is quite sensitive to their distribution on the parametric plane. We present a new approach where a polygonal (quadrilateral or triangular) surface is extracted from the segmented image. This surface is subsequently projected onto a parametric plane in a manner to ensure a one-to-one mapping. The resulting polygonal mesh is then regularized for area and edge length. Finally, from this point, surface fitting is relatively trivial. The novelty of our approach lies in the regularization of the polygonal mesh. Process performance is assessed with the reconstruction of a geometric model of mouse heart ventricles from a computerized tomography scan. Our results show an excellent reproduction of the geometric data with surfaces that areC2continuous.
Overview on Topical 5-ALA Photodynamic Therapy Use for Non Melanoma Skin Cancers
Authors: Cantisani Carmen , Paolino Giovanni , Faina Valentina , Frascani Federica , Cantoresi Franca , Bianchini Daniela , Fazia Gilda , Calvieri Stefano
Published: March 2014

Ultraviolet radiation (UV) contributes to a variety of skin diseases including inflammation, degenerative aging, and cancer. Historically, humans have been exposed to UV radiation mainly through occupational exposure; recreational UV exposure, however, has increased dramatically in recent years, because of outdoor leisure activities and to purposely tan for cosmetic purposes. Both UVB and UVA radiation have been shown to cause DNA damage and immunosuppression, the important forms of biological damage that lead to NMSC. Nonmelanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized which continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include photodynamic therapy, electrochemotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Among these, photodynamic therapy is a noninvasive technique with excellent cosmetic outcome and good curative results, when used in initial stages of skin cancers for superficial lesions. It is administered under numerous and significantly varied regimens and there are a wide range of cure rates reported, permitting treatment of large and multiple lesions with excellent cosmetic results. This is an overview of photodynamic applications especially for the treatment of NMSC, with a short focus on daylight modality.
Fault Diagnosis for Compensating Capacitors of Jointless Track Circuit Based on Dynamic Time Warping
Authors: Dong Wei
Published: March 2014

Aiming at the problem of online fault diagnosis for compensating capacitors of jointless track circuit, a dynamic time warping (DTW) based diagnosis method is proposed in this paper. Different from the existing related works, this method only uses the ground indoor monitoring signals of track circuit to locate the faulty compensating capacitor, not depending on the shunt current of inspection train, which is an indispensable condition for existing methods. So, it can be used for online diagnosis of compensating capacitor, which has not yet been realized by existing methods. To overcome the key problem that track circuit cannot obtain the precise position of the train, the DTW method is used for the first time in this situation to recover the function relationship between receiver’s peak voltage and shunt position. The necessity, thinking, and procedure of the method are described in detail. Besides the classical DTW based method, two improved methods for improving classification quality and reducing computation complexity are proposed. Finally, the diagnosis experiments based on the simulation model of track circuit show the effectiveness of the proposed methods.
Differential Speed Rolling to Reduce Warping in Bimetallic Slab
Authors: Lee C. H. , Park J. P. , Moon Y. H.
Published: March 2014

The mismatch of lengthwise elongation due to the difference of deformation resistances between constituent materials of bimetallic slab can cause warping. As the warping of bimetallic slab can lead to poor product shape with reduced productivity, this study focuses on the effect of differential speed rolling on the reduction of warping. The effects of differential speed rolling on the reduction of curvature are mainly performed by FEM based on fundamental processing parameters. Differential speed rolling experiments by using low-weight Al1050/Al6061 bimetallic slab produced by continuous clad casting have also been performed for the validation purpose. As rolling experiments for numerous processing conditions are hard to achieve, limited number of experiments has been performed in this study. Simulation results based on parametric study provide a broad overview on the warping behavior in Al1050/Al6061 bimetallic slab rolling.
A Simplified Predictive Control of Constrained Markov Jump System with Mixed Uncertainties
Authors: Yin Yanyan , Liu Yanqing , Karimi Hamid R.
Published: March 2014

A simplified model predictive control algorithm is designed for discrete-time Markov jump systems with mixed uncertainties. The mixed uncertainties include model polytope uncertainty and partly unknown transition probability. The simplified algorithm involves finite steps. Firstly, in the previous steps, a simplified mode-dependent predictive controller is presented to drive the state to the neighbor area around the origin. Then the trajectory of states is driven as expected to the origin by the final-step mode-independent predictive controller. The computational burden is dramatically cut down and thus it costs less time but has the acceptable dynamic performance. Furthermore, the polyhedron invariant set is utilized to enlarge the initial feasible area. The numerical example is provided to illustrate the efficiency of the developed results.
An ImprovedPhysarum polycephalumAlgorithm for the Shortest Path Problem
Authors: Zhang Xiaoge , Wang Qing , Adamatzky Andrew , Chan Felix T. S. , Mahadevan Sankaran , Deng Yong
Published: March 2014

Shortest path is among classical problems of computer science. The problems are solved by hundreds of algorithms, silicon computing architectures and novel substrate, unconventional, computing devices. Acellular slime mouldP. polycephalumis originally famous as a computing biological substrate due to its alleged ability to approximate shortest path from its inoculation site to a source of nutrients. Several algorithms were designed based on properties of the slime mould. Many of thePhysarum-inspired algorithms suffer from a low converge speed. To accelerate the search of a solution and reduce a number of iterations we combined an original model of Physarum-inspired path solver with a new a parameter, called energy. We undertook a series of computational experiments on approximating shortest paths in networks with different topologies, and number of nodes varying from 15 to 2000. We found that the improvedPhysarumalgorithm matches well with existing Physarum-inspired approaches yet outperforms them in number of iterations executed and a total running time. We also compare our algorithm with other existing algorithms, including the ant colony optimization algorithm and Dijkstra algorithm.