bluuebunny/crossref_metadata_2025 huggingface dataset:
WITNESS AGREEMENT AND THE TRUTH‐CONDUCIVENESS OF COHERENTIST JUSTIFICATION
Authors: ROCHE WILLIAM
Published: March 2012

abstract

Some recent work in formal epistemology shows that “witness agreement” by itself implies neither an increase in the probability of truth nor a high probability of truth—the witnesses need to have some “individual credibility.” It can seem that, from this formal epistemological result, it follows that coherentist justification (i.e., doxastic coherence) is not truth‐conducive. I argue that this does not follow. Central to my argument is the thesis that, though coherentists deny that there can be noninferential justification, coherentists do not deny that there can be individual credibility.
ON THE COHERENCE OF HIGHER‐ORDER BELIEFS
Authors: SCHUBERT STEFAN , OLSSON ERIK J.
Published: March 2012

abstract

Let us by ‘first‐order beliefs’ mean beliefs about the world, such as the belief that it will rain tomorrow, and by ‘second‐order beliefs’ let us mean beliefs about the reliability of first‐order, belief‐forming processes. In formal epistemology, coherence has been studied, with much ingenuity and precision, for sets of first‐order beliefs. However, to the best of our knowledge, sets including second‐order beliefs have not yet received serious attention in that literature. In informal epistemology, by contrast, sets of the latter kind play an important role in some respectable coherence theories of knowledge and justification. In this paper, we extend the formal treatment of coherence to second‐order beliefs. Our main conclusion is that while extending the framework to second‐order beliefs sheds doubt on the generality of the notorious impossibility results for coherentism, another problem crops up that might be no less damaging to the coherentist project: facts of coherence turn out to be epistemically accessible only to agents who have a good deal of insight into matters external to their own belief states.
Tick-Borne Encephalitis Virus-Neutralizing Antibodies in Different Immunoglobulin Preparations
Authors: Rabel Philip O. , Planitzer Christina B. , Farcet Maria R. , Kreil Thomas R.
Published: March 2012

Patients with primary immunodeficiency (PIDs) depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG). Using the tick-borne encephalitis virus (TBEV), geographic variability in IVIG antibody content was shown. Care should therefore be exercised when treating PIDs in a given geography, as only locally sourced plasma contains the antibody specificities against the circulating pathogens in the given locality.
Streptococcus pseudopneumoniae Identification by Pherotype: a Method To Assist Understanding of a Potentially Emerging or Overlooked Pathogen
Authors: Leung Marcus H. , Ling Clare L. , Ciesielczuk Holly , Lockwood Julianne , Thurston Sarah , Charalambous Bambos M. , Gillespie Stephen H.
Published: March 2012

The recent identification of
Streptococcus pseudopneumoniae
(pseudopneumococcus) has complicated classification schemes within members of the “mitis” streptococcal group. Accurate differentiation of this species is necessary for understanding its disease potential and identification in clinical settings. This work described the use of the competence-stimulatory peptide ComC sequence for identification of
S. pseudopneumoniae
. ComC sequences from clinical sources were determined for 17 strains of
S. pseudopneumoniae
,
Streptococcus pneumoniae
, and
Streptococcus oralis
. An additional 58 ComC sequences from a range of sources were included to understand the diversity and suitability of this protein as a diagnostic marker for species identification. We identified three pherotypes for this species, delineated CSP6.1 (10/14, 79%), CSP6.3 (3/14, 21%), and SK674 (1/14, 7%). Pseudopneumococcal ComC sequences formed a discrete cluster within those of other oral streptococci. This suggests that the
comC
sequence could be used to identify
S. pseudopneumoniae
, thus simplifying the study of the pathogenic potential of this organism. To avoid confusion between pneumococcal and pseudopneumococcal pherotypes, we have renamed the competence pherotype CSP6.1, formerly reported as an “atypical” pneumococcus, CSPps1 to reflect its occurrence in
S. pseudopneumoniae
.
Helper Virus-Independent Transcription and Multimerization of a Satellite RNA Associated with Cucumber Mosaic Virus
Authors: Choi Soon Ho , Seo Jang-Kyun , Kwon Sun-Jung , Rao A. L. N.
Published: March 2012

Satellite RNAs are the smallest infectious agents whose replication is thought to be completely dependent on their helper virus (HV). Here we report that, when expressed autonomously in the absence of HV, a variant of satellite RNA (satRNA) associated with
Cucumber mosaic virus
strain Q (Q-satRNA) has a propensity to localize in the nucleus and be transcribed, generating genomic and antigenomic multimeric forms. The involvement of the nuclear phase of Q-satRNA was further confirmed by confocal microscopy employing
in vivo
RNA-tagging and double-stranded-RNA-labeling assays. Sequence analyses revealed that the Q-satRNA multimers formed in the absence of HV, compared to when HV is present, are distinguished by the addition of a template-independent heptanucleotide motif at the monomer junctions within the multimers. Collectively, the involvement of a nuclear phase in the replication cycle of Q-satRNA not only provides a valid explanation for its persistent survival in the absence of HV but also suggests a possible evolutionary relationship to viroids that replicate in the nucleus.
Valosin-Containing Protein (VCP/p97) Is Required for Poliovirus Replication and Is Involved in Cellular Protein Secretion Pathway in Poliovirus Infection
Authors: Arita Minetaro , Wakita Takaji , Shimizu Hiroyuki
Published: March 2012

Poliovirus (PV) modifies membrane-trafficking machinery in host cells for its viral RNA replication. To date, ARF1, ACBD3, BIG1/BIG2, GBF1, RTN3, and PI4KB have been identified as host factors of enterovirus (EV), including PV, involved in membrane traffic. In this study, we performed small interfering RNA (siRNA) screening targeting membrane-trafficking genes for host factors required for PV replication. We identified valosin-containing protein (VCP/p97) as a host factor of PV replication required after viral protein synthesis, and its ATPase activity was essential for PV replication. VCP colocalized with viral proteins 2BC/2C and 3AB/3B in PV-infected cells and showed an interaction with 2BC and 3AB but not with 2C and 3A. Knockdown of VCP did not suppress the replication of coxsackievirus B3 or Aichi virus. A VCP-knockdown-resistant PV mutant had an A4881G (a mutation of E253G in 2C) mutation, which is known as a determinant of a secretion inhibition-negative phenotype. However, knockdown of VCP did not affect the inhibition of cellular protein secretion caused by overexpression of each individual viral protein. These results suggested that VCP is a host factor required for viral RNA replication of PV among membrane-trafficking proteins and provides a novel link between cellular protein secretion and viral RNA replication.
Restored PB1-F2 in the 2009 Pandemic H1N1 Influenza Virus Has Minimal Effects in Swine
Authors: Pena Lindomar , Vincent Amy L. , Loving Crystal L. , Henningson Jamie N. , Lager Kelly M. , Lorusso Alessio , Perez Daniel R.
Published: March 2012

PB1-F2 is an 87- to 90-amino-acid-long protein expressed by certain influenza A viruses. Previous studies have shown that PB1-F2 contributes to virulence in the mouse model; however, its role in natural hosts—pigs, humans, or birds—remains largely unknown. Outbreaks of domestic pigs infected with the 2009 pandemic H1N1 influenza virus (pH1N1) have been detected worldwide. Unlike previous pandemic strains, pH1N1 viruses do not encode a functional PB1-F2 due to the presence of three stop codons resulting in premature truncation after codon 11. However, pH1N1s have the potential to acquire the full-length form of PB1-F2 through mutation or reassortment. In this study, we assessed whether restoring the full-length PB1-F2 open reading frame (ORF) in the pH1N1 background would have an effect on virus replication and virulence in pigs. Restoring the PB1-F2 ORF resulted in upregulation of viral polymerase activity at early time points
in vitro
and enhanced virus yields in porcine respiratory explants and in the lungs of infected pigs. There was an increase in the severity of pneumonia in pigs infected with isogenic virus expressing PB1-F2 compared to the wild-type (WT) pH1N1. The extent of microscopic pneumonia correlated with increased pulmonary levels of alpha interferon and interleukin-1β in pigs infected with pH1N1 encoding a functional PB1-F2 but only early in the infection. Together, our results indicate that PB1-F2 in the context of pH1N1 moderately modulates viral replication, lung histopathology, and local cytokine response in pigs.
Tacaribe Virus Causes Fatal Infection of An Ostensible Reservoir Host, the Jamaican Fruit Bat
Authors: Cogswell-Hawkinson Ann , Bowen Richard , James Stephanie , Gardiner David , Calisher Charles H. , Adams Rick , Schountz Tony
Published: March 2012

Tacaribe virus (TCRV) was first isolated from 11
Artibeus
species bats captured in Trinidad in the 1950s during a rabies virus surveillance program. Despite significant effort, no evidence of infection of other mammals, mostly rodents, was found, suggesting that no other vertebrates harbored TCRV. For this reason, it was hypothesized that TCRV was naturally hosted by artibeus bats. This is in stark contrast to other arenaviruses with known hosts, all of which are rodents. To examine this hypothesis, we conducted experimental infections of Jamaican fruit bats (
Artibeus jamaicensis
) to determine whether they could be persistently infected without substantial pathology. We subcutaneously or intranasally infected bats with TCRV strain TRVL-11573, the only remaining strain of TCRV, and found that low-dose (10
4
50% tissue culture infective dose [TCID
50
]) inoculations resulted in asymptomatic and apathogenic infection and virus clearance, while high-dose (10
6
TCID
50
) inoculations caused substantial morbidity and mortality as early as 10 days postinfection. Uninoculated cage mates failed to seroconvert, and viral RNA was not detected in their tissues, suggesting that transmission did not occur. Together, these data suggest that
A. jamaicensis
bats may not be a reservoir host for TCRV.
Protective Role of Interferon Regulatory Factor 3-Mediated Signaling against Prion Infection
Authors: Ishibashi Daisuke , Atarashi Ryuichiro , Fuse Takayuki , Nakagaki Takehiro , Yamaguchi Naohiro , Satoh Katsuya , Honda Kenya , Nishida Noriyuki
Published: March 2012

Abnormal prion protein (PrPSc) generated from the cellular isoform of PrP (PrPC) is assumed to be the main or sole component of the pathogen, called prion, of transmissible spongiform encephalopathies (TSE). Because PrP is a host-encoded protein, acquired immune responses are not induced in TSE. Meanwhile, activation of the innate immune system has been suggested to partially block the progression of TSE; however, the mechanism is not well understood. To further elucidate the role of the innate immune system in prion infection, we investigated the function of interferon regulatory factor 3 (IRF3), a key transcription factor of the MyD88-independent type I interferon (IFN) production pathway. We found that IRF3-deficient mice exhibited significantly earlier onset with three murine TSE strains, namely, 22L, FK-1, and murine bovine spongiform encephalopathy (mBSE), following intraperitoneal transmission, than with wild-type controls. Moreover, overexpression of IRF3 attenuated prion infection in the cell culture system, while PrPScwas increased in prion-infected cells treated with small interfering RNAs (siRNAs) against IRF3, suggesting that IRF3 negatively regulates PrPScformation. Our findings provide new insight into the role of the host innate immune system in the pathogenesis of prion diseases.
Decreased Neuraminidase Activity Is Important for the Adaptation of H5N1 Influenza Virus to Human Airway Epithelium
Authors: Ilyushina Natalia A. , Bovin Nicolai V. , Webster Robert G.
Published: March 2012

Highly pathogenic avian H5N1 influenza viruses remain a pandemic threat. Antiviral drugs such as neuraminidase (NA) inhibitors will be crucial for disease control in the event of a pandemic. Should drug-resistant H5N1 viruses develop, all defense strategies will be compromised. To determine the likelihood and mechanisms of emergence of NA inhibitor-resistant H5N1 variants in humans, we serially passaged two H5N1 viruses, A/Hong Kong/213/03 and A/Turkey/65-1242/06, in normal human bronchial epithelial (NHBE) cells in the presence of oseltamivir, zanamivir, or peramivir. To monitor the emergence of changes associated with the adaptation of H5N1 viruses to humans, we passaged the strains in the absence of drugs. Under pressure of each NA inhibitor, A/Turkey/65-1242/06 developed mutations in the hemagglutinin (HA) (H28R and P194L/T215I) and NA (E119A) proteins that reduced virus binding to α2,3-sialyl receptor and NA activity. Oseltamivir pressure selected a variant of A/Hong Kong/213/03 virus with HA P194S mutation that decreased viral binding to α2,6 receptor. Under peramivir pressure, A/Hong Kong/213/03 virus developed a novel NA mutation, R156K, that reduced binding to all three drugs, caused about 90% loss of NA activity, and compromised replication in NHBE cells. Both strains were eliminated in NHBE cells when they were cultivated in the absence of drugs. Here, we show for the first time that decreased NA activity mediated through NA inhibitors is essential for the adaptation of pandemic H5N1 influenza virus to humans. This ability of decreased NA activity to promote H5N1 infection underlines the necessity to optimize management strategies for a plausible H5N1 pandemic.
Small-Molecule Inhibition of Human Immunodeficiency Virus Type 1 Replication by Targeting the Interaction between Vif and ElonginC
Authors: Zuo Tao , Liu Donglai , Lv Wei , Wang Xiaodan , Wang Jiawen , Lv Mingyu , Huang Wenlin , Wu Jiaxin , Zhang Haihong , Jin Hongwei , Zhang Liangren , Kong Wei , Yu Xianghui
Published: March 2012

The HIV-1 viral infectivity factor (Vif) protein is essential for viral replication. Vif recruits cellular ElonginB/C-Cullin5 E3 ubiquitin ligase to target the host antiviral protein APOBEC3G (A3G) for proteasomal degradation. In the absence of Vif, A3G is packaged into budding HIV-1 virions and introduces multiple mutations in the newly synthesized minus-strand viral DNA to restrict virus replication. Thus, the A3G-Vif-E3 complex represents an attractive target for development of novel anti-HIV drugs. In this study, we identified a potent small molecular compound (VEC-5) by virtual screening and validated its anti-Vif activity through biochemical analysis. We show that VEC-5 inhibits virus replication only in A3G-positive cells. Treatment with VEC-5 increased cellular A3G levels when Vif was coexpressed and enhanced A3G incorporation into HIV-1 virions to reduce viral infectivity. Coimmunoprecipitation and computational analysis further attributed the anti-Vif activity of VEC-5 to the inhibition of Vif from direct binding to the ElonginC protein. These findings support the notion that suppressing Vif function can liberate A3G to carry out its antiviral activity and demonstrate that regulation of the Vif-ElonginC interaction is a novel target for small-molecule inhibitors of HIV-1.
Influenza Virus H1N1pdm09 Infections in the Young and Old: Evidence of Greater Antibody Diversity and Affinity for the Hemagglutinin Globular Head Domain (HA1 Domain) in the Elderly than in Young Adults and Children
Authors: Verma Nitin , Dimitrova Milena , Carter Donald M. , Crevar Corey J. , Ross Ted M. , Golding Hana , Khurana Surender
Published: March 2012

The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. We performed in-depth evaluation of antibody responses generated following H1N1pdm09 infection of naïve ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). In addition to hemagglutination inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display libraries (GFPDL) to evaluate the antibody repertoires against internal genes, hemagglutinin (HA), and neuraminidase (NA) and also measured antibody affinity for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets demonstrated gradual development of antibody repertoires with a focus on M1 and HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70 years old) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) than for the younger age groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1) (but not HA2) than those from younger subjects (50% versus <22% 7 M urea resistance, respectively) and lower antibody dissociation rates using surface plasmon resonance. This is the first study in humans that provides evidence for a qualitatively superior antibody response in the elderly following H1N1pdm09 infection, indicative of recall of long-term memory B cells or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.
Myocardial infarction with normal coronaries: an autopsy perspective
Authors: Silvanto Anna , de Noronha Sofia Victoria , Sheppard Mary N
Published: March 2012

Aim

To analyse postmortem cases of myocardial infarction (MI) with normal coronary arteries in terms of patient characteristics, features of the MI and risk factors.

Methods

This retrospective non-case controlled study was carried out at a specialist cardiac pathology department at a tertiary cardiac referral centre. Cases of histologically confirmed MI and normal coronary arteries during the period 1996–2010 were identified and analysed for the presence of risk factors.

Results

Nineteen cases of histologically confirmed MI and normal coronary arteries were identified with a similar gender ratio 1:1.1 (male:female) and mean age of 33±12 years (range 14–58). All patients died suddenly. The location of the infarct was variable, with left anterior descending artery territory being the single most prevalent (47%). Risk factors were identified in the majority of cases (n=14), with some cases experiencing more than one association, including alcohol and/or predominately class A drug use (n=7), including cocaine, inflammation (n=2), hypercoagulable state (n=3) and exertion (n=2).

Conclusions

Current data regarding prognosis in MI with normal coronary arteries suggests a favourable outcome in the context of major cardiovascular events. No large series of fatal cases have been reported. This study highlights that this entity can be fatal and its prognosis may be less favourable than currently considered. This autopsy series also demonstrates that the causation of MI with normal coronary arteries is complex and multifactorial, including a history of alcohol and/or drug use. It also highlights the importance of accurate epidemiological data from referring pathologists.
Phylogenetic relationships among the polyploid and diploidAegilopsspecies inferred from the nuclear 5S rDNA sequences (Poaceae: Triticeae)
Authors: Baum B.R. , Edwards T. , Mamuti M. , Johnson D.A.
Published: March 2012

Phylogenetic inferences of the polyploid Aegilops taxa were drawn based upon the analysis of 909 nuclear 5S rDNA sequences obtained from 15 Aegilops polyploid taxa (531 sequences new to this paper) and 378 sequences from our previous study on the diploid taxa. The 531 sequences can be split into two orthologous groups (unit classes), the long AE1 and short AE1 previously identified in the diploid set. An examination of the relationships between unit classes and their associated haplomes suggests that U haplome sequences found in Ae. umbellulata are the closest to the T sequences found in Amblyopyrum muticum and that sequences of the polyploid species expected to be the M type found in Ae. comos are more similar to the T haplome sequences, except in the three hexaploids Ae. glumiaristata, Ae. juvenalis, and Ae. vavilovii and the tetraploid Ae. crassa where they are found to be similar to the M haplome sequences. These three hexaploid taxa likely originated from the tetraploid Ae. crassa (DM), while the closest taxon to the fourth hexaploid, Ae. recta, is the tetraploid Ae. neglecta (UM). Based upon the distribution of the unit classes, several reticulate phylogenies depicting evolutionary relationships among diploid, tetraploid, and hexaploid taxa were constructed; however, none of these widely used methods could depict the expected reticulate relationship as previously drawn from cytogenetic analyses in this group of allopolyploid species. These results suggest that evolutionary relationships derived from models based upon the assumption of bifurcating species require careful interpretation when these same models are applied to species with reticulate evolution.
Widespread atypical mitochondrial DNA structure in isopods (Crustacea, Peracarida) related to a constitutive heteroplasmy in terrestrial species
Authors: Doublet Vincent , Raimond Roland , Grandjean Frédéric , Lafitte Alexandra , Souty-Grosset Catherine , Marcadé Isabelle
Published: March 2012

Metazoan mitochondrial DNA (mtDNA) is generally composed of circular monomeric molecules. However, a few exceptions do exist and among them two terrestrial isopods Armadillidium vulgare and Porcellionides pruinosus have an atypical mtDNA composed of linear monomers associated with circular “head-to-head” dimers: a very unusual structure for animal mtDNA genome. To assess the distribution of this atypical mtDNA among isopods, we performed RFLP and Southern blot analyses on mtDNA of 16 terrestrial (Oniscidea family) and two aquatic isopod species: the marine Sphaeroma serratum (suborder Flabellifera, sister group of Oniscidea) and the freshwater Asellus aquaticus (Asellota, early derived taxon of isopod). The atypical mtDNA structure was observed in 15 terrestrial isopod species and A. aquaticus, suggesting a wide distribution of atypical mtDNA among isopods. However, a typical metazoan mtDNA structure was detected in the marine isopod S. serratum and the Oniscidea Ligia oceanica . Our results suggest two possible scenarios: an early origin of the atypical mtDNA in isopods followed by reversion to the typical ancestral mtDNA structure for several species, or a convergent appearance of the atypical mtDNA structure in two isopod suborders. We compare this distribution of the atypical mtDNA structure with the presence of a heteroplasmy also observed in the mtDNA of several terrestrial isopod species. We discuss if this transmitted heteroplasmy is vectored by the atypical mtDNA and its impact on the maintenance of the atypical mtDNA in isopods.
THE HEAT-KERNEL MOST-LIKELY-PATH APPROXIMATION
Authors: GATHERAL JIM , WANG TAI-HO
Published: March 2012

In this article, we derive a new most-likely-path (MLP) approximation for implied volatility in terms of local volatility, based on time-integration of the lowest order term in the heat-kernel expansion. This new approximation formula turns out to be a natural extension of the well-known formula of Berestycki, Busca and Florent. Various other MLP approximations have been suggested in the literature involving different choices of most-likely-path; our work fixes a natural definition of the most-likely-path. We confirm the improved performance of our new approximation relative to existing approximations in an explicit computation using a realistic S&P500 local volatility function.
Palaeogeographic consequences of conservational models in the South Atlantic Ocean
Authors: Aslanian Daniel , Moulin Maryline
Published: March 2012

Conservational models, like simple shear, pure shear or polyphase models that exclude exchanges between the lower continental crust and upper mantle, are usually proposed to explain the lithospheric stretching and consequent crustal thinning of passive continental margins. These models need large amounts of horizontal movement, and have, therefore, important implications for plate kinematic reconstructions and intraplate deformation. In this paper we propose to show these implications in the Central Segment of the South Atlantic Ocean. In the Angola–Brazilian system, these models imply about 240 km of horizontal movement. This movement can be compensated by two end-member mechanisms: (1) an intraplate deformation located in Africa; and (2) an intraplate deformation located in South America. We detail for each solution the strong geological and geodynamical implications, and discuss the consequences for the genesis of passive continental margins.
Role of catalase on the hypoxia/reoxygenation stress in the hypoxia-tolerant Nile tilapia
Authors: Welker Alexis F. , Campos Élida G. , Cardoso Luciano A. , Hermes-Lima Marcelo
Published: March 2012

The specific contribution of each antioxidant enzyme to protection against the reoxygenation-associated oxidative stress after periods of hypoxia is not well understood. We assessed the physiological role of catalase during posthypoxic reoxygenation by the combination of two approaches. First, catalase activity of Nile tilapias ( Oreochromis niloticus ) was 90% suppressed by intraperitoneal injection of 3-amino-1,2,4-triazole (ATZ, 1g/kg). In ATZ-injected fish, liver GSH levels, oxidative stress markers, and activities of other antioxidant enzymes remained unchanged. Second, animals with depleted catalase activity (or those saline-injected) were subjected to a cycle of severe hypoxia (dissolved O2= 0.28 mg/l for 3 h) followed by reoxygenation (0.5 to 24 h). Hypoxia did not induce changes in the above-mentioned parameters, either in saline- or in ATZ-injected animals. Reoxygenation increased superoxide dismutase activity in saline-injected fish, whose levels were similar to ATZ-injected animals. The activities of glutathione S-transferase, selenium-dependent glutathione peroxidase, and total-GPX and the levels of GSH-eq, GSSG, and thiobarbituric acid reactive substances remained unchanged during reoxygenation in both saline- and ATZ-injected fish. The GSSG/GSH-eq ratio in ATZ-injected fish increased at 30 min of reoxygenation compared with saline-injected ones. Reoxygenation also increased carbonyl protein levels in saline-injected fish, whose levels were similar to the ATZ-injected group. Our work shows that inhibition of liver tilapia catalase causes a redox imbalance during reoxygenation, which is insufficient to induce further oxidative stress. This indicates the relevance of hepatic catalase for hypoxia/reoxygenation stress in tilapia fish.
Differential regulation of circulating and renal ACE2 and ACE in hypertensive mRen2.Lewis rats with early-onset diabetes
Authors: Yamaleyeva Liliya M. , Gilliam-Davis Shea , Almeida Igor , Brosnihan K. Bridget , Lindsey Sarah H. , Chappell Mark C.
Published: March 2012

We examined the impact of early diabetes on the circulating and kidney renin-angiotensin system (RAS) in male and female mRen2.Lewis (mRen2) hypertensive rats. Diabetes (DB) was induced by streptozotocin (STZ; 65 mg/kg) at 11 wk of age for 4 wk without insulin replacement. Systolic blood pressures were not increased in DB males or females compared with controls (CON). Circulating angiotensin-converting enzyme 2 (ACE2) increased ninefold ( P < 0.05) in DB females and threefold ( P < 0.05) in DB males, but circulating ACE and ANG II were higher in the DB groups. Serum C-reactive protein was elevated in DB females but not DB males, and the vascular responses to acetylcholine and estradiol were attenuated in the DB females. Proteinuria, albuminuria, and angiotensinogen excretion increased to a similar extent in both DB females and males. Glomerular VEGF expression also increased to a similar extent in both DB groups. Renal inflammation (CD68+cells) increased only in DB females although males exhibited greater inflammation that was not different with DB. Cortical ACE2 did not change in DB females but was reduced (30%) in DB males. Renal neprilysin activity (>75%, P < 0.05) was markedly reduced in the DB females to that in the DB and CON males. ACE activity was significantly lower in both female (75%, P < 0.05) and male (50%; P < 0.05) DB groups, while cortical ANG II and Ang-(1-7) levels were unchanged. In conclusion, female mRen2 rats are not protected from vascular damage, renal inflammation, and kidney injury in early STZ-induced diabetes despite a marked increase in circulating ACE2 and significantly reduced ACE within the kidney.
Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons
Authors: Leao Ricardo M. , Li Shuang , Doiron Brent , Tzounopoulos Thanos
Published: March 2012

Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba2+-sensitive, inwardly rectifying potassium conductance (Kir). Variability in Kir maximal conductance causes variations in the resting membrane potential (RMP). Low Kir conductance depolarizes RMP to voltages above the threshold for activating subthreshold-persistent sodium channels (Nap). Once Nap channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information.
Proinflammatory Characteristics of SMAC/DIABLO-Induced Cell Death in Antitumor Therapy
Authors: Emeagi Perpetua U. , Van Lint Sandra , Goyvaerts Cleo , Maenhout Sarah , Cauwels Anje , McNeish Iain A. , Bos Tomas , Heirman Carlo , Thielemans Kris , Aerts Joeri L. , Breckpot Karine
Published: March 2012

Molecular mimetics of the caspase activator second mitochondria-derived activator of caspase (SMAC) are being investigated for use in cancer therapy, but an understanding of in vivo effects remains incomplete. In this study, we offer evidence that SMAC mimetics elicit a proinflammatory cell death in cancer cells that engages an adaptive antitumor immune response. Cancer cells of different histologic origin underwent apoptosis when transduced with lentiviral vectors encoding a cytosolic form of the SMAC mimetic LV-tSMAC. Strikingly, treatment of tumor-bearing mice with LV-tSMAC resulted in the induction of apoptosis, activation of antitumor immunity, and enhanced survival. Antitumor immunity was accompanied by an increase of tumor-infiltrating lymphocytes displaying low PD-1 expression, high lytic capacity, and high levels of IFN-γ when stimulated. We also noted in vivo a decrease in regulatory T cells along with in vitro activation of tumor-specific CD8+ T cells by dendritic cells (DC) isolated from tumor draining lymph nodes. Last, tumor-specific cytotoxic T cells were also found to be activated in vivo. Mechanistic analyses showed that transduction of cancer cells with LV-tSMAC resulted in exposure of calreticulin but not release of HMGB1 or ATP. Nevertheless, DCs were activated upon engulfment of dying cancer cells. Further validation of these findings was obtained by their extension in a model of human melanoma using transcriptionally targeted LV-tSMAC. Together, our findings suggest that SMAC mimetics can elicit a proinflammatory cell death that is sufficient to activate adaptive antitumor immune responses in cancer. Cancer Res; 72(6); 1342–52. ©2012 AACR.
Value of High Frequency Ultrasonography in Diagnosis and Surgical Repair of Traumatic Finger Tendon Ruptures
Authors: Zhang Gai-Ying , Zhuang Hai-Ying , Wang Le-Xin
Published: March 2012

Objective: To investigate the value of high frequency ultrasonography in the diagnosis of zone 2 flexor tendon injuries. Subjects and Methods: Ninety-two patients (49 males and 43 females, mean age 32.6 ± 11.2 years) with zone 2 flexor tendon injuries in one or more digits were randomly divided into a study (n = 46, 95 digits) and a control group (n = 46, 90 digits). In the study group, preoperative ultrasound was performed and surgical repair was conducted based on ultrasonographic findings. Diagnosis and surgical repair of the control group was based on history of trauma and physical examination. Results: Types of ruptures (complete or partial) and the location of the distal end of the ruptured tendon diagnosed by preoperative ultrasonography were consistent with surgical findings in all cases (95/95, 100%) of the study group, whereas the concordance rate between clinically diagnosed ruptures and surgical findings was only 34.4% (31/90) in the control group (p = 0.02). Conclusion: Preoperative high frequency ultrasound examination yielded excellent diagnostic accuracy for zone 2 flexor tendon injuries.
Adipose Tissue Inflammation and Adiponectin Resistance in Patients With Advanced Heart Failure
Authors: Khan Raffay S. , Kato Tomoko S. , Chokshi Aalap , Chew Michael , Yu Shuiqing , Wu Christina , Singh Parvati , Cheema Faisal H. , Takayama Hiroo , Harris Collette , Reyes-Soffer Gissette , Knöll Ralph , Milting Hendrik , Naka Yoshifumi , Mancini Donna , Schulze P. Christian
Published: March 2012

Background—

Heart failure (HF) is characterized by inflammation, insulin resistance, and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF.

Methods and Results—

Circulating insulin, adiponectin, leptin, and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy control subjects. Serum adiponectin was higher in HF patients before VAD implantation compared with control subjects (13.3±4.9 versus 6.4±2.1 μg/mL,
P
=0.02). VAD implantation (mean, 129±99 days) reduced serum adiponectin (7.4±3.4 μg/mL,
P
<0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 6.3±5.8–3.6±2.9;
P
<0.05). Adiponectin expression in adipose tissue decreased after VAD implantation (−65%;
P
<0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared with control subjects and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared with control subjects (1999±24 μm
2
versus 5583±142 μm
2
in control subjects;
P
<0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared with control subjects (+25%;
P
<0.01), which normalized after VAD implantation.

Conclusions—

Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation, and adiponectin resistance in patients with advanced HF.
Shirts Today, Skins Tomorrow
Authors: Cunningham Kathleen Gallagher , Bakke Kristin M. , Seymour Lee J. M.
Published: March 2012

While theoretical models of conflict often treat actors as unitary, most self-determination groups are fragmented into a number of competing internal factions. This article presents a framework for understanding the “dual contests” that self-determination groups engage in—the first with their host state and the second between co-ethnic factions within groups. Using a new data set of the number of factions within a sample of self-determination groups from 1960 to 2008, the authors find that competition between co-ethnic factions is a key determinant of their conflict behavior. More competing factions are associated with higher instances of violence against the state as well as more factional fighting and attacks on co-ethnic civilians. More factions using violence increases the chances that other factions will do so, and the entry of a new faction prompts violence from existing factions in a within-group contest for political relevance. These findings have implications for both theory and policy.
Local Responses to a Global Downturn: Labour Adjustment in Two Multinational Companies
Authors: Clibborn Stephen
Published: March 2012

After years of steadily declining sales and profits, the global financial crisis sent the United States and Australian automotive manufacturing industries into crises of their own. Faced with dramatically reduced demand, the companies cut production and, consequently, their production workforces. Using qualitative data from case studies of the Ford Motor Company, the General Motors Company and their wholly owned Australian subsidiaries, Ford Australia and Holden, we can assess the extent to which these two multinational companies standardized their methods of adjusting labour levels and to what extent such responses were localized. In four manufacturing plants implementing similar cuts in production, responses were developed locally, shaped largely by local market, institutional and political forces.
Industrial Agency in Regional Trades and Labour Councils
Authors: Steel Kathryn M
Published: March 2012

The range of roles and activities undertaken by peak union bodies has recently been conceptualized by Ellem and Shields. This article uses their framework to discuss industrial agency in an Australian regional peak union council. An examination of two locally significant industrial campaigns using historical data specifically considers the impact of the industrial identity developed within the particular locale. These campaigns support the proposal that regional peak union council agency is determined by the geographic and social relationships resulting from local industrial history. In addition, in order to achieve successful outcomes for campaigns, even over local issues, forms of agency should be flexible and operate across scales. This article concludes that extending the Ellem and Shields framework to include more explicit consideration of locale and specific industrial identity as a mediating factor enables a greater understanding of not only the possible roles and functions of, but also those developed in practice by, regional peak union bodies.
Caring in a Small Urban High School
Authors: Rivera-McCutchen Rosa L.
Published: March 2012

This article focuses on a small urban high school that developed a culture devoted to caring for their historically underserved students. Interviews with school founders, teachers, and alumni, as well as observations of classrooms and professional activities, revealed the high school attended to the affective needs of their students, which improved attendance and graduation rates, but often neglected to hold students to high academic standards, which led to future underperformance. The article concludes that, absent a fundamental belief that students are capable of high-quality work, other forms of caring are insufficient.
Processes of Political Socialization
Authors: Lee Nam-Jin , Shah Dhavan V. , McLeod Jack M.
Published: March 2012

By analyzing data from a national panel survey of adolescents (ages 12-17) and their parents conducted around the 2008 general election, this study explores the varied roles communication plays in socializing youth into democratic citizenship. In particular, we propose and test a communication mediation model of youth socialization, in which interdependent communication processes located in the family, schools, media, and peer networks combine to cultivate communication competence, a set of basic communication skills and motives needed for active and informed participation in public life. Analysis of our panel data indicates that participation in deliberative classroom activities and democratic peer norms contribute to civic activism among youth. These peer and school influences, however, are found to be largely indirect, working through informational use of conventional and online news media, and expression and discussion of political ideas outside of classroom and family boundaries. In particular, our findings highlight strong online pathways to participation, centering on news consumption and political expression via digital media technologies, suggesting the key role of the Internet in this dynamic.
Regime Stability in Post-1986 Uganda
Authors: Rwengabo Sabastiano
Published: March 2012

Uganda suffered coups between 1966 and 1985, but has remained stable since 1986 despite predisposition to previous coups. Ethnic antagonism, weak state institutionalization, and past coups, had made Uganda coup-prone. Compared to previous governments, the post-1986 leadership effectively applied and undertook coup-prevention strategies consistent with James Quinlivan’s coup-proofing theory. These include establishing a parallel military structure to the mainstream military; formation of security services with parallel reporting channels, monitoring over society, and other security agencies; and co-optation of the military in politics through parliamentary representation. These measures have helped the regime to watch over security agencies and prevent possible military intervention. Uganda’s post-1986 regime stability is interesting in its own right. But it provides evidence consistent with, and useful for testing the efficacy of, Quinlivan’s coup-proofing theory: with relevant application and domestication the theory applies to Uganda.
Bridging informal tagging and formal semantics via hybrid navigation
Authors: Lezcano Leonardo , García-Barriocanal Elena , Sicilia Miguel-Angel
Published: March 2012

The folksonomies resulting from user-generated tag systems feature rapid adaptability, and reflect the information needs of their supporting user communities. However, they suffer from well-known problems, such as polysemy, heteronymy and lack of recall, which have been addressed in controlled vocabularies and ontologies, which in turn follow slower but more controlled evolution processes. These differences have led to the bridging approach described in this paper, which is based on mapping tags to ontology elements. Mappings can be automatically generated or explicitly provided by user-created assertions between tags and ontology elements. The main objective is to combine existing tag navigation, such as that featured in Delicious, with related tag recommendations obtained from ontology relations, in order to provide a hybrid navigation context that benefits folksonomy browsing. The implementation of such integration, combining Delicious and the OpenCyc knowledge base, is described, along with an evaluation of its potential in improving navigation through the user-generated tag system. The results reveal that the new semantic shortcuts and the decrease in dead ends can substantially influence the collaborative bookmarking experience.
Racial Diversity, Racial Asymmetries, and Team Learning Environment: Effects on Performance
Authors: Ely Robin J. , Padavic Irene , Thomas David A.
Published: March 2012

This paper argues that learning in cross-race interactions is critical for work teams to realize performance benefits from racial diversity but that diversity is a liability when society’s negative stereotypes about racial minorities’ competence inhibit such interactions. We analyze two years of data from 496 retail bank branches to investigate racial asymmetries in the dynamics of team learning and their impact on the link between diversity and bottom-line performance. As expected, minorities’ negative assessments of their team’s learning environment precipitate a negative relationship between diversity and performance, irrespective of White teammates’ assessments; only when both groups view the team’s learning environment as supportive—implying that the team has successfully countered the negative effects of societal stereotypes on cross-race learning—is the relationship positive. We conclude that acknowledging the impact of societal asymmetries between racial groups, especially in regard to learning, can reorient research about the link between identity-group-based diversity and performance.
Dynamic visual servoing from sequential regions of interest acquisition
Authors: Dahmouche Redwan , Andreff Nicolas , Mezouar Youcef , Ait-Aider Omar , Martinet Philippe
Published: March 2012

One of the main drawbacks of vision-based control that remains unsolved is the poor dynamic performances caused by the low acquisition frequency of the vision systems and the time latency due to processing. We propose in this paper to face the challenge of designing a high-performance dynamic visual servo control scheme. Two versatile control laws are developed in this paper: a position-based dynamic visual servoing and an image-based dynamic visual servoing. Both control laws are designed to compute the control torques exclusively from a sequential acquisition of regions of interest containing the visual features to achieve an accurate trajectory tracking. The presented experiments on vision-based dynamic control of a high-speed parallel robot show that the proposed control schemes can perform better than joint-based computed torque control.
Chiari 2 Without Spinal Dysraphism: Does It Blow a Hole in the Pathogenesis?
Authors: Citton Valentina , Toldo Irene , Balao Laura , Pettenazzo Andrea , Emanuelli Enzo , Sartori Stefano , Calderone Milena , Manara Renzo
Published: March 2012

Chiari malformation type 2 is characterized by hindbrain protrusion and a constellation of supratentorial malformations. Chiari malformation type 2 is thought to be causally related to myelomeningocele due to intrauterine cerebrospinal fluid overdrainage. This relationship is so strong that it has become a rule. A 14-year-old girl affected by mental retardation, spastic triparesis, and epilepsy is presented. Brain magnetic resonance imaging disclosed a severe Chiari malformation type 2, whereas spine magnetic resonance imaging was unremarkable. The authors discuss previous literature describing rare cases of Chiari malformation type 2 without open spinal dysraphism and the relevance of concomitant, sometimes overlooked, neuroimaging findings, underlying how exceptions might be hurdles but might also eventually strengthen the rules.
Mortality Risk After Neonatal Seizures in Very Preterm Newborns
Authors: Pisani Francesco , Copioli Cristiana , Turco Emanuela Claudia , Sisti Lisa , Cossu Giuseppe , Seri Stefano
Published: March 2012

We analyzed clinical and instrumental data of 403 consecutive newborns with gestational age from 24 to 32 weeks, admitted to the University-Hospital of Parma between January 2000 and December 2007, to evaluate the possible relationship between neonatal mortality and occurrence of neonatal seizures in very preterm newborns. Seventy-four subjects died during hospital stay. Seizures were present in 35 neonates, in whom the mortality rate was 37.1%. Multivariate analysis revealed that birth-weight <1000 g (odds ratio: 4.48; 95% confidence interval: 1.47-13.68; P < .01), cardiopulmonary resuscitation (odds ratio: 5.35; 95% confidence interval: 1.19-23.98; P = .02), and moderately and severely abnormal cerebral ultrasound scan findings (odds ratio: 2.48; 95% confidence interval: 1.02-6.05; P < .04; odds ratio: 9.56; 95% confidence interval: 3.45-26.51; P < .01, respectively) were related to the in-hospital mortality but not the presence of neonatal seizures. Our study suggests that neonatal seizures alone are not an independent risk factor for early death in very preterm newborns.